Nitric oxide (NO) is a gaseous signaling molecule involved in various physiological processes in horses. It is produced by nitric oxide synthase enzymes and plays a role in vascular regulation, immune response, and neurotransmission. In equine physiology, nitric oxide contributes to the modulation of blood flow, particularly in the respiratory and cardiovascular systems. It also influences inflammatory responses and can impact muscle function. This page compiles peer-reviewed research studies and scholarly articles that explore the production, function, and implications of nitric oxide in equine health and disease.
We evaluated the vasorelaxant effect of propentofylline (PPF), a methylxanthine derivative, and its mechanism of action in equine digital veins (EDVs). Cumulative concentration-response curves to PPF (1 nM-300 µM) were recorded in phenylephrine-precontracted EDV rings under different experimental conditions. PPF-induced relaxation was partially inhibited by endothelium removal, but was unaltered by CGS-15943 (an adenosine receptor antagonist; 3 µM). PPF-induced relaxation was partially inhibited in the presence of L-NAME (a nitric oxide (NO) synthase inhibitor; 100 µM), ODQ (an inhibitor of...
Galvão AM, Szóstek AZ, Skarzynski DJ, Ferreira-Dias GM.Normal reproductive function involves the expression of inflammatory mediators. Regarding the corpus luteum (CL), cytokines promote the cross-talk between immune, vascular and steroidogenic cells, among others. Moreover, TNF, IFNG and FASL were shown to regulate equine CL establishment and regression. We hypothesized that cytokines action on equine CL may be mediated by nitric oxide (NO), through the regulation of endothelial NO synthase (eNOS) expression. TNF increased eNOS mRNA level and NO metabolite (nitrite) production during CL growth. Cytokines combined action (TNF+IFNG+FASL) promoted e...
Grubb T, Frendin JH, Edner A, Funkquist P, Hedenstierna G, Nyman G.Anaesthetized horses commonly become hypoxaemic due to ventilation/perfusion (V·A/Q·) mismatch and increased pulmonary shunt fraction (Qs·/Qt·). Pulse-delivered inhaled nitric oxide may improve oxygenation but may increase plasma concentration of the potent vasoconstrictor, endothelin-1 (ET-1). Objectives: Study 1) compare arterial oxygen concentration (PaO2) and saturation (SaO2), calculated Qs·/Qt· and ET-1 concentration; and Study 2) assess V·A/Q· matching and measured Qs·/Qt· in isoflurane-anaesthetized horses in left lateral recumbency receiving pulse-delivered inhaled nitric ox...
Cathcart MP, Love S, Sutton DG, Reardon RJ, Hughes KJ.Analyses of exhaled breath (EB) and exhaled breath condensate (EBC) are non-invasive modalities for assessing the lower airways but these methods have not been applied to Thoroughbred racehorses in training. The aims of this study were to determine whether EB and EBC could be obtained from Thoroughbred racehorses in the field and to investigate the effects of exercise per se and during different ambient temperatures and humidity on exhaled concentrations of nitric oxide (eNO), carbon monoxide (eCO) and EBC pH. EB and EBC samples were obtained from 28 Thoroughbred racehorses pre- and post-exerc...
Olver CS, Nielsen VG.Carboxyheme and metheme states modulate hemostasis in humans and other species. Further, carbon monoxide and/or nitric oxide production increase in inflammatory disorders involving the gastrointestinal tract, with associated hypercoagulability or hypocoagulability. In particular, the horse suffers both thrombotic or coagulopathic complications during acute gastrointestinal disease. This investigation characterized the thrombelastographic response to carboxyheme (via CORM-2) or metheme (via phenylhydroxylamine, PHA) states without/with addition of tissue type plasminogen activator. Citrated pla...
Woodward EM, Christoffersen M, Campos J, Horohov DW, Scoggin KE, Squires E, Troedsson MH.The first objective of this study was to evaluate intrauterine nitric oxide (NO) and endometrial inducible NO synthase (iNOS) in mares susceptible or resistant to persistent breeding-induced endometritis (PBIE) within 24 h after breeding. Mares susceptible (n = 6) or resistant (n = 6) to PBIE were inseminated over five cycles, and uterine secretions and endometrial biopsies were collected before and 2, 6, 12 and 24 h after insemination. Uterine secretions were analysed for NO and biopsies were analyzed for iNOS expression. A second experiment evaluated the effect of treatment with dexame...
Galvão A, Valente L, Skarzynski DJ, Szóstek A, Piotrowska-Tomala K, Rebordão MR, Mateus L, Ferreira-Dias G.Regulation of immune-endocrine interactions in the equine endometrium is not fully understood. The aims of the present study were to: (1) investigate the presence of tumour necrosis factor alpha (TNF), interferon gamma (IFNG), Fas ligand (FASLG) and their receptors in the mare endometrium throughout the oestrous cycle; and (2) assess endometrial secretory function (prostaglandins), angiogenic activity and cell viability in response to TNF, oestradiol (E2), progesterone (P4) and oxytocin (OXT). Transcription of TNF and FASLG mRNA increased during the early and late luteal phase (LP), whereas IF...
Kwok WH, Ho EN, Leung GN, Wong AS, Yue SK, Wan TS.Relaxin (RLX) is a peptide hormone belonging to the relaxin-like peptide family. Relaxin-2 (RLX-2), a heteromeric polypeptide consisting of an A-chain (24 amino acids) and a B-chain (29 amino acids) linked together by two inter-chain disulfide bonds, is the main circulating RLX hormone in human. Due to its ability to dilate blood vessels surrounding the smooth muscles via induction of nitric oxide resulting in the increase of blood and oxygen supplies to the muscles, it may enhance athletic performance and is therefore banned in horseracing, equestrian competitions, and human sports. In order ...
Grubb T, Edner A, Frendin JH, Funkquist P, Rydén A, Nyman G.To assess oxygenation, ventilation-perfusion (V/Q) matching and plasma endothelin (ET-1) concentrations in healthy horses recovering from isoflurane anaesthesia administered with or without pulse-delivered inhaled nitric oxide (iNO). Methods: Prospective experimental trial. Methods: Healthy adult Standardbred horses. Methods: Horses were anaesthetized with isoflurane in oxygen and placed in lateral recumbency. Six control (C group) horses were anaesthetized without iNO delivery and six horses received pulse-delivered iNO (NO group). After 2.5 hours of anaesthesia isoflurane and iNO were abrupt...
Nyman G, Grubb TL, Heinonen E, Frendin J, Edner A, Malavasi LM, Frostell C, Högman M.The study aimed to investigate the effect of varying pulse lengths of inhaled nitric oxide (iNO), and 2.5 hours of continuous pulse-delivered iNO on pulmonary gas exchange in anaesthetized horses. Methods: Experimental study. Methods: Six Standardbred horses. Methods: Horses received acepromazine, detomidine, guaifenesin, thiopentone and isoflurane in oxygen, were positioned in dorsal recumbency and were breathing spontaneously. iNO was on average pulsed during the first 20, 30, 43 or 73% of the inspiration in 15 minute steps. The pulse length that corresponded to the highest (peak) partial pr...
Carrade DD, Lame MW, Kent MS, Clark KC, Walker NJ, Borjesson DL.Mesenchymal stem cells (MSCs) derived from bone marrow (BM), adipose tissue (AT), umbilical cord blood (CB), and umbilical cord tissue (CT) are increasingly being used to treat equine inflammatory and degenerative lesions. MSCs modulate the immune system in part through mediator secretion. Animal species and MSC tissue of origin are both important determinants of MSC function. In spite of widespread clinical use, how equine MSCs function to heal tissues is fully unknown. In this study, MSCs derived from BM, AT, CB, and CT were compared for their ability to inhibit lymphocyte proliferation and ...
Pearson W, Fletcher RS, Kott LS.A biological extract of high-rosmarinic acid mint (HRAM) has previously demonstrated inhibitory effects on lipopolysaccharide (LPS)-induced prostaglandin E(2) (PGE(2)), nitric oxide (NO) and glycosaminoglycan (GAG) release in vitro. This study was undertaken to determine whether HRAM added to feed produces similar effects in horses challenged with intra-articular LPS. Eight horses received HRAM (0 or 28.1 ± 1.3 g/day; n = 4 per group) in their feed for 24 days in a blinded manner. On day 21, all horses received an intra-articular injection of LPS (0.3 ng) into their left or right intercarpal ...
Kabbesh N, Gogny M, Chatagnon G, Noireaud J, Thorin C, Desfontis JC, Mallem MY.The direct vasodilatory action of pentoxifylline (1-(5-oxohexyl)-3,7-dimethylxanthine) and its signalling pathway was evaluated in equine digital veins. Cumulative concentration-response curves to pentoxifylline (1 nM to 300 μM) were recorded in phenylephrine-precontracted equine digital vein rings under different experimental conditions. Relaxation to pentoxifylline was partially inhibited by endothelium removal, but was unaltered by CGS-15943 (a non-xanthine adenosine receptor antagonist; 3 μM). Nitric oxide synthase (NOS), soluble guanylate cyclase and cyclooxygenase (COX) inhibitors (Nω...
Artese L, Piattelli A, Di Stefano DA, Piccirilli M, Pagnutti S, D'Alimonte E, Perrotti V.The aim of the present study was to perform a comparative histological and immunohistochemical evaluation of microvessel density, vascular endothelial growth factor, and nitric oxide synthase (NOS) expression in sinus augmentation using autologous bone alone or in combination with equine bone. Methods: Sixteen patients underwent sinus augmentation with autologous bone and a 50:50 mixture of autologous and equine bone. Control cores were harvested from preexisting nonaugmented bone under the sinus floor. The specimens were processed for immunohistochemistry. Results: The greatest values of micr...
Williams CA, Burk AO.Dietary intake and feeding management practices could affect the degree of physiological stress and subsequent performance of high level 3-day event horses. Objective: To assess whether a relationship exists between dietary intake levels of selected nutrients and the inflammatory and antioxidant status in horses competing in a high level 3-day event. Methods: Riders competing in a CCI2*/CCI3* 3-day event (n = 35) answered a nutritional management survey conducted by the investigators at the competition. Actual and recommended intakes of vitamin E, potassium (K), calcium (Ca), phosphorus (P) an...
el-Ashker MR.The present study was carried out to evaluate the role of oxidative stress in the pathophysiologic process of acute renal failure associated with exertional rhabdomyolysis (ER) in Egyptian horses. ER was tentatively diagnosed in 31 Baladi horses based on case history, physical examination findings and confirmed by elevation of plasma creatine kinase (CK) and urine myoglobin concentrations. According to severity of the condition, the diseased horses were categorized into two main groups; the first group included 18 horses with minimal clinical signs and plasma CK <60 000 IU/L; whereas, the seco...
Ranjithkumar M, Kamili NM, Saxena A, Dan A, Dey S, Raut SS.Oxidant/antioxidant equilibrium disturbance has already been reported in trypanosome infections by several authors. The present study was aimed to explore the possible oxidant/antioxidant disturbance in surra of naturally infected horses before and after treatment. Fifteen naturally infected horses were chosen to analyse erythrocytic indices, platelet counts, lipid peroxides (LPO), nitric oxide (NO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) while six healthy animals acted as control. There was a highly significant (P<0.001) reduction in red blood cell (RBC) c...
Hurley DJ, Berghaus LJ, Hurley KA, Moore JN.To evaluate effects of black walnut extract (BWE) on equine mononuclear cells and determine whether BWE has direct proinflammatory effects. Methods: Mononuclear cells separated from blood samples from 8 horses. Methods: Aqueous BWE was prepared and processed to eliminate contamination with particulates and microbes. A Limulus amoebocyte lysate assay was used to detect lipopolysaccharide (LPS) contamination in the BWE. Mononuclear cells were incubated in minimal essential medium with or without the addition of 0.6% to 10% (vol/vol) BWE. These mononuclear cells were assessed for viability, activ...
Casella S, Giannetto C, Giudice E, Piccione G.The objective of the present study was to evaluate the platelet response to different workload in athletic horse and the influence of hydrocortisone on this response. For this purpose, six Sella Italiana gelding athletic horses, ranging in age from 8 to 10 years and clinically healthy, were subjected to four different exercises: horse-walker, treadmill, obstacle course of 1.00 m and obstacle course of 1.25 m. From all the horses, citrated plasma samples were collected at rest, immediately after exercise and 30 min after the end of the exercise to assess the maximum degree of platelet aggregati...
Honnens A, Weisser S, Welter H, Einspanier R, Bollwein H.The objective of this study was to investigate the relationships between uterine perfusion and estrogen, progesterone and the uterine nitric oxide synthase (NOS) system in five trotter mares during the estrous cycle. Color Doppler sonography for measurement of uterine blood flow and collection of blood for determination of plasma estrogen and progesterone concentrations were performed on days 0 (= ovulation), 1, 5, 11 and 15 and daily during estrus (days -1 to -4) of one estrous cycle; endometrial biopsy collection for mRNA expression analysis of NOS and estrogen receptors was performed on day...
Ferreira-Dias G, Costa AS, Mateus L, Korzekwa AJ, Galvão A, Redmer DA, Lukasik K, Szóstek AZ, Woclawek-Potocka I, Skarzynski DJ.Cytokines and nitric oxide (NO) are potential mediators of luteal development and maintenance, angiogenesis, and blood flow. The aim of this study was to evaluate (i) the localization and protein expression of endothelial and inducible nitric oxide synthases (eNOS and iNOS) in equine corpora lutea (CL) throughout the luteal phase and (ii) the effect of a nitric oxide donor (spermine NONOate, NONOate) on the production of progesterone (P4) and prostaglandin (PG) E(2) and factor(s) that stimulate endothelial cell proliferation using equine luteal explants. Luteal tissue was classified as corpora...
Novensa L, Selent J, Pastor M, Sandberg K, Heras M, Dantas AP.Conjugated equine estrogen therapy is the most common hormone replacement strategy used to treat postmenopausal women. However, the ability of an individual conjugated equine estrogen to modulate NO production and, therefore, to induce cardiovascular protection is largely unknown. The effects of equine and naturally occurring estrogens on NO generation were evaluated in human aortic endothelial cells by measuring in vivo NO production, as well as NO synthase (eNOS) activity and expression. The transcriptional activity on the eNOS gene was determined by the ability of estrogen receptors (alpha ...
Ascenzi P, di Masi A, Gullotta F, Mattu M, Ciaccio C, Coletta M.Cyanide binds to ferric heme-proteins with a very high affinity, reflecting the very low dissociation rate constant (k(off)). Since no techniques are available to estimate k(off), we report herewith a method to determine k(off) based on the irreversible reductive nitrosylation reaction to trap ferric myoglobin (Mb(III)). The k(off) value for cyanide dissociation from ferric cyanide horse heart myoglobin (Mb(III)-cyanide) was determined at pH 9.2 and 20.0 degrees C. Mixing Mb(III)-cyanide and NO solutions brings about absorption spectral changes reflecting the disappearance of Mb(III)-cyanide w...
Yi J, Heinecke J, Tan H, Ford PC, Richter-Addo GB.It is now well-established that mammalian heme proteins are reactive with various nitrogen oxide species and that these reactions may play significant roles in mammalian physiology. For example, the ferrous heme protein myoglobin (Mb) has been shown to reduce nitrite (NO(2)(-)) to nitric oxide (NO) under hypoxic conditions. We demonstrate here that the distal pocket histidine residue (His64) of horse heart metMb(III) (i.e., ferric Mb(III)) has marked effects on the mode of nitrite ion coordination to the iron center. X-ray crystal structures were determined for the mutant proteins metMb(III) H...
Carmona JU, Argüelles D, Deulofeu R, Martínez-Puig D, Prades M.The aim of this study was to evaluate the clinical and biochemical effects of the administration of oral hyaluronan (Hyal-Joint [HJ]) on young horses with osteochondrosis (OC). Our hypotheses were that HJ administration is safe, would decrease the degree of synovial effusion and the concentration of nitric oxide (NO) and prostaglandin E2 (PGE2) in synovial fluid, and would increase the concentration of hyaluronic acid (HA) in plasma and synovial fluid. Eleven young horses with tarsocrural OC were included in a randomised, double-blinded, placebo-controlled pilot clinical trial. Six horses rece...
Ueno D, Yabuki A, Obi T, Shiraishi M, Nishio A, Miyamoto A.We investigated the effect of bradykinin (BK) on isolated equine basilar arterial rings with and without endothelium. BK induced concentration-dependent contraction of resting arterial rings and no relaxation when the rings were precontracted by prostaglandin F(2alpha). The maximal response and pD(2) value were 161.2 +/- 28.1% (to 60 mm KCl-induced contraction) and 8.24 +/- 0.25 respectively. The cumulative concentration-response curve for BK was not shifted to the right by des-Arg(9)-[Leu(8)]-BK (a B(1)-receptor antagonist), HOE140 (a B(2)-receptor antagonist) or NPC567 (another B(2)-receptor...
Ortega Ferrusola C, González Fernández L, Macías García B, Salazar-Sandoval C, Morillo Rodríguez A, Rodríguez Martinez H, Tapia JA, Peña FJ.The ability of stallion spermatozoa to produce nitric oxide (NO) before (fresh) and after freezing and thawing (FT) was evaluated by means of flow cytometry after loading the sperm suspension with the probe, 4,5-diaminofluorescenin diacetate. The presence of NO synthase (NOS) was investigated by Western blotting using anti-NOS1, anti-NOS3, or anti-universal NOS antibodies (Abs). While NO was detected both in fresh and FT sperm suspensions, its production increased after cryopreservation only when egg yolk was removed from the extender. Anti-NOS1 Ab intensively labeled a single band with an app...
Doherty TJ.Surgical manipulation of the intestines activates intestinal macrophages that release cytokines and nitric oxide, which results in inhibition of intestinal motility. Subsequent infiltration of circulating leukocytes into the intestinal wall contributes to cytokine and nitric oxide release and exacerbates ileus. Other factors contributing to ileus are endotoxemia; edema of the intestine wall subsequent to excessive fluid therapy; hypocalcemia; and long abdominal incisions. Because treatment of ileus with prokinetic drugs has not proven to be very effective, efforts should be directed at reducin...
Pearson W, Orth MW, Lindinger MI.To evaluate inflammatory responses induced via intra-articular recombinant human interleukin (IL)-1beta treatment in horses receiving a dietary nutraceutical (DN; composed of mussel, shark cartilage, abalone, and Biota orientalis lipid extract) and assess the clinical effects of long-term DN administration. Methods: 22 healthy horses. Methods: 12 horses were fed 0, 15, 45, or 75 mg of DN (3 horses/treatment) daily for 84 days. General health and clinicopathologic variables were monitored at intervals. Ten other horses received 0 or 15 g of DN/d (5 horses/treatment) for 29 days (beginning day -...
Chiocchetti R, Bombardi C, Mongardi-Fantaguzzi C, Venturelli E, Russo D, Spadari A, Montoneri C, Romagnoli N, Grandis A.This paper describes the morphology and distribution of the enteric nervous system (ENS) cells and fibres immunoreactive for choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), substance P (SP), calcitonin gene-related peptide (CGRP), NF200kDa (NF200), and S100 protein. The percentages of subclasses of enteric neurons in the total neuronal population were investigated by the use of anti-PGP 9.5 or anti-NSE antibodies. ChAT-IR myenteric plexus (MP) and submucosal plexus (SMP) neurons were 66+/-7% and 74+/-15%, respectively, whereas those cells expressing nNOS-IR were 38+/-7...
MacEachern KE, Smith GL, Nolan AM.Equine endothelial cells were isolated from the pulmonary artery by enzymatic digestion and grown to confluency. The cells were characterised by positive immunofluorescent staining for von Willebrand factor and NADPH-diaphorase staining for nitric oxide synthase. Measurements of endothelins indicated that there were significant release rates from the cells for up to six hours. Measurements of intracellular calcium concentration showed that the application of bradykinin caused a transient increase in calcium concentration with similar characteristics to those observed in other endothelial cell ...
Bird JL, Wells T, Platt D, Bayliss MT.Proteoglycan degradation was induced in young equine articular cartilage explants cultured for eight days in the presence of 50 ng/ml recombinant human interleukin-1 beta. Degradation was initiated after 6 hours of exposure to the cytokine. This was accompanied by an induction of nitric oxide synthesis and a decrease in the incorporation of [36S]sulphate into the glycosaminoglycan chains of proteoglycans. The addition of 1mM N-iminoethyl-L-ornithine (an inhibitor of nitric oxide synthase) to the explant cultures in the presence of rhIL-1 beta suppressed the synthesis of NO and restored proteog...
Moore RM, Sedrish SA, Holmes EP, Koch CE, Venugopal CS.The objective of this study was to determine and compare the in vitro responses of equine large colon arterial and venous rings to vasodilatory neuropeptides; calcitonin gene-related peptide (CGRP); substance P (SP); vasoactive intestinal polypeptide (VIP); and acetylcholine (ACh), a standard nonpeptide endothelium-dependent vasodilator. Responses of vessel rings to graded concentrations (10(-11) M to 10(-5) M) of each drug were determined in endothelium-intact, denuded, and Nomega-nitro-L-arginine methyl ester (L-NAME, 10(-5) M)-treated rings that were pre-contracted with norepinephrine. Perc...
Recio P, López PG, Hernández M, Prieto D, Contreras J, García-Sacristán A.The involvement of nitric oxide (NO) and the mechanisms mediating neurogenic relaxation were investigated in the horse corpus cavernosum. NADPH-diaphorase activity was expressed in nerve fibres around arteries and muscular bundles in the horse trabecular tissue. Relaxations in response to electrical field stimulation were tetrodotoxin (10(-6) M)-sensitive, indicating their neurogenic origin. The NO synthase inhibitor, L-NO-arginine (L-NO-Arg, 3 x 10(-5) M), abolished the electrically induced relaxations, which were significantly reversed by L-arginine (3 x 10(-3) M). Exogenous NO (10(-6)-10(-3...
Lindinger MI.This paper reviews the limits to exercise imposed by increases in ambient, hypothalamic, and contracting skeletal muscle temperature in humans and horses. Like humans, horses frequently compete in hot environments, yet their high mass-specific rate of heat production and low mass-specific surface area for heat dissipation places them at a great disadvantage compared to humans. Exercise in hot conditions increases the rate of body heat storage and reduces the time required to reach a critical hypothalamic temperature that results in voluntary fatigue. This critical temperature appears to be ass...
Zoller D, Lüttgenau J, Steffen S, Bollwein H.Poor uterine perfusion has been proposed as a cause of infertility in mares. The objective of this study was to investigate the effect of isosorbide dinitrate (ISDN), a nitric oxide donor, on uterine and ovarian blood flow resistance during diestrus and early pregnancy in mares. Six Trotter mares, aged 7 to 14 years, were examined daily during the first 11 days of three diestrous periods, and five of those mares were also examined during the first 11 days of two pregnancies. Six mares randomly received a placebo, a low dose (30 mg, ISDN30), or a high dose of ISDN (60 mg, ISDN60) through t...
Fenton JI, Chlebek-Brown KA, Caron JP, Orth MW.Glucosamine inhibits recombinant human interleukin-1 stimulated cartilage degradation in equine cartilage explants. Recently, recombinant equine interleukin-1 has been cloned and purified. Therefore, the objective of this study was to characterise the effects of glucosamine on indices of cartilage degradation in recombinant equine IL-1beta-stimulated equine articular cartilage explants. Cartilage discs were harvested from the weight-bearing region of the articular surface of the antebrachiocarpal and middle carpal joints of horses (age 2-8 years) and cultured under standard conditions. Explant...
Baxter GM.Low doses of endotoxin cause vasoconstriction and hypoperfusion of the digit, small intestine, and cecum in horses. To determine the potential cause of these vascular alterations, in vitro vascular responses of palmar digital arteries and veins were determined in 8 horses after intravenous (IV) infusion of 1 L 0.9% NaCl (control) and 0.1 microgram/kg Escherichia coli 055:B5 endotoxin in 1 L of 0.9% NaCl (endotoxin-treated). Vessels were surgically removed under general anesthesia, cut into 4-mm vascular rings, suspended in tissue baths, and attached to force displacement transducers for measur...
Khan FA, Chenier TS, Foster RA, Hewson J, Scholtz EL.Emerging research suggests that the nitric oxide system may play a role in persistent breeding-induced endometritis (PBIE) in the mare. Differences in uterine nitric oxide (NO) levels between mares susceptible or resistant to PBIE and a dose-dependent inhibitory effect of NO on uterine contractility have been demonstrated. The objectives of this study were to investigate the difference in total nitric oxide synthase (NOS) activity of the endometrium between susceptible and resistant mares and the effect of a specific inducible nitric oxide synthase (iNOS) inhibitor on the endometrial NOS activ...
Obi T, Kabeyama A, Nishio A.In coronary arterial rings isolated from horses, 10(-8)-10(-6) mol/l acetylcholine (ACh) induced concentration-dependent contractions which were potentiated by the removal of endothelium and by pretreatment with L-nitro-arginine (LNAG) or methylene blue (MB). Relatively lower concentrations of ACh (10(-14)-10(-8) mol/l) induced relaxation when the coronary rings were contracted by phenylephrine (PE). ACh-induced contractions in the coronary rings without endothelium were competitively inhibited by each muscarinic subtype selective antagonist in the following order of potency: 4-diphenylacetoxy...
Bourebaba N, Sikora M, Qasem B, Bourebaba L, Marycz K.Equine metabolic syndrome (EMS), which encompasses insulin resistance, low-grade inflammation and predisposition to laminitis is a critical endocrine disorder among the most prevalent conditions affecting horses from different breeds. According to the most recent research, low human sex hormone-binding globulin (SHBG) serum levels correlate with an increased risk of obesity, insulin resistance and diabetes, and may contribute to overall metabolic dysregulations. This study aimed to test whether exogenous SHBG could protect EMS affected adipose-derived stromal stem cells (EqASC) from apoptosis,...
Li P, Sun S, Zhang W, Ouyang W, Li X, Yang K.The objective of this study was to evaluate the effects of pre-exercise -citrulline supplementation on the athletic performance of speed-racing horses during a high-intensity exercise. On the 20th day of the experiment, blood samples were collected at 3 h and 6 h post-supplementation to measure the amino acid and polyamine concentrations. On the 38th day of the experiment, the horses participated in a 2000 m speed race, and three distinct blood samples were gathered for assessing blood gases, hematological parameters, the plasma biochemistry, antioxidant parameters, and NO concentrations. The...
Hunter RP.Inflammation is a process consisting of a complex of cytological and chemical reactions which occur in and around affected blood vessels and adjacent tissues in response to an injury caused by a physical, chemical or biological insult. Much work has been performed in the past several years investigating inducible nitric oxide synthase (NOS, EC 1.14.13.39) and nitric oxide in inflammation. This has resulted in a rapid increase in knowledge about iNOS and nitric oxide. Nitric oxide formation from inducible NOS is regulated by numerous inflammatory mediators, often with contradictory effects, dep...
van der Harst M, Bull S, Brama PA, Barneveld AB, van Weeren PR, van de Lest C.Osteoarthritis (OA) is a chronic debilitating joint disorder in which the importance of inflammation is increasingly recognized. In advanced cases, both the articular cartilage and the underlying bony layers are affected, but the exact sequence of events and their localization in the initial phase of pathogenesis remain uncertain. We measured nitric oxide (NO) end products in tissue layers that constitute the bearing surface of the joint, as possible indicators of physiological and pathological processes. Methods: Nitrite as a measure for NO and nitrotyrosine was measured in articular cartilag...
von Rechenberg B, McIlwraith CW, Akens MK, Frisbie DD, Leutenegger C, Auer JA.Nitric oxide (NO), prostaglandin E2 (PGE2), and the activity of neutral metalloproteinases (NMPs) were measured in conditioned media of equine synovial membrane and articular cartilage explant cultures from horses with normal joints (n = 7) and from horses affected with moderate (n = 7) or severe osteoarthritis (n = 14) as judged by macroscopic appearance. Normal articular cartilage appeared glossy and bluish-white, was of normal thickness and showed no evidence of discolouration, fibrillation or other cartilage discontinuity. Slight discolouration and fibrillation or minor clefts of the carti...
Saastamoinen M, Särkijärvi S, Suomala H.Six Finnhorse mares were used in a digestibility trial, in which six typical horse diets were compared. The diets were: (A) haylage 100%; (B) hay 100%; (C) hay 70% and oats 30%; (D) hay 70% and soybean meal + oats 30%; (E) hay 70%, rapeseed meal + oats 30% and (F) hay 70 %, linseed meal + oats 30%. The trial was conducted according to an unbalanced 6 × 4 Latin square design with four 3-week experimental periods. The experimental period consisted of 17-day preliminary feeding which was followed by a 4-day total faecal and urine collection periods to evaluate N excretion. The digestibilities of...
Ueno D, Yabuki A, Obi T, Shiraishi M, Nishio A, Miyamoto A.We investigated the effect of bradykinin (BK) on isolated equine basilar arterial rings with and without endothelium. BK induced concentration-dependent contraction of resting arterial rings and no relaxation when the rings were precontracted by prostaglandin F(2alpha). The maximal response and pD(2) value were 161.2 +/- 28.1% (to 60 mm KCl-induced contraction) and 8.24 +/- 0.25 respectively. The cumulative concentration-response curve for BK was not shifted to the right by des-Arg(9)-[Leu(8)]-BK (a B(1)-receptor antagonist), HOE140 (a B(2)-receptor antagonist) or NPC567 (another B(2)-receptor...
Khan FA, Chenier TS, Murrant CL, Foster RA, Hewson J, Scholtz EL.Nitric oxide (NO) may have a role in persistent breeding-induced endometritis in mares through an inhibitory effect on uterine contractility. The objectives of this study were to test the effect of NO on spontaneous uterine contractility in-vitro and to evaluate whether this effect varied between the longitudinal and circular muscle layers of the uterus. Reproductive tracts were collected from eight euthanized non-pregnant mares (age 4-19 years; body weight 405-530 kg). Transrectal examination of the reproductive tract was performed before euthanasia to evaluate stage of the estrous cycle and...
Bourebaba L, Zyzak M, Sikora M, Serwotka-Suszczak A, Mularczyk M, Al Naem M, Marycz K.Sex hormone binding globulin (SHBG) deteriorated expression has been recently strongly correlated to increased level of circulating pro-inflammatory cytokines and insulin resistance, which are typical manifestations of equine metabolic syndrome (EMS). Despite previous reports demonstrated the potential therapeutic application of SHBG for liver-related dysfunctions, whether SHBG might modulate equine adipose-derived stem/stromal cells (EqASCs) metabolic machinery remains unknown. Therefore, we evaluated for the first time the impact of SHBG protein on metabolic changes in ASCs isolated from hea...
Roberto da Costa RP, Costa AS, Korzekwa AJ, Platek R, Siemieniuch M, Galvão A, Redmer DA, Silva JR, Skarzynski DJ, Ferreira-Dias G.Nitric oxide (NO) plays an important role in prostaglandin secretion and angiogenesis in the reproductive system. In the present study, the roles of the NO donor spermine NONOate and tumour necrosis factor-alpha (TNF; as a positive control) in prostaglandin production and angiogenic activity of equine endometria during the oestrous cycle were evaluated. In addition, the correlation between NO production and the expression of key prostaglandin synthase proteins was determined. The protein expression of prostaglandin F synthase (PGFS) increased in early and mid-luteal stages, whereas that of pro...
Carmona JU, Argüelles D, Deulofeu R, Martínez-Puig D, Prades M.The aim of this study was to evaluate the clinical and biochemical effects of the administration of oral hyaluronan (Hyal-Joint [HJ]) on young horses with osteochondrosis (OC). Our hypotheses were that HJ administration is safe, would decrease the degree of synovial effusion and the concentration of nitric oxide (NO) and prostaglandin E2 (PGE2) in synovial fluid, and would increase the concentration of hyaluronic acid (HA) in plasma and synovial fluid. Eleven young horses with tarsocrural OC were included in a randomised, double-blinded, placebo-controlled pilot clinical trial. Six horses rece...
Galvin N, Collins D.: This report presented a brief overview of the literature on the perinatal asphyxia syndrome (PAS) in foals as a prelude to a description of the investigation and treatment of acute onset seizures in a 24-hour-old Thoroughbred colt foal.PAS can cause a wide variety of clinical abnormalities, of which seizures due to encephalopathy are the most significant. The structural and biochemical components of CNS neurones are disrupted by the shift from oxidative to anaerobic metabolism, with a resultant deficit in cellular energy. The cells succumb to the combined effects of acidosis, neurotoxic acti...
The Journal of physiologySeptember 15, 1996
Volume 495 ( Pt 3), Issue Pt 3 863-874 doi: 10.1113/jphysiol.1996.sp021638
Mills PC, Marlin DJ, Demoncheaux E, Scott C, Casas I, Smith NC, Higenbottam T.1. The effects of exercise on the production rate of nitric oxide (NO) in exhaled air (VNO) and the effects of inhaled NO (80 p.p.m.) on cardiovascular and respiratory parameters were investigated in five Throughbred horses. 2. The concentration of NO ([NO]) in exhaled air collected from within the nasal opening was lower when collected at a high flow rate of 80 l min-1 than at a low flow rate of 20 l min-1: when trotting at 3.7 m s-1 the values were 0.78 +/- 0.15 and 1.23 +/- 9.14 p.p.b., respectively, and when cantering at 9 m s-1 the values were 1.69 +/- 0.31 and 2.25 +/- 0.32 p.p.b., respe...
Zhu FX, Zhang XY, Olszewski MA, Robinson NE.The effects of capsaicin and neuropeptides were examined in equine tracheal smooth muscle (TSM). Neither capsaicin nor substance P (SP) contracted TSM. Capsaicin (100 microM) elicited relaxation in TSM contracted with methacholine. This relaxation was not mimicked by SP or calcitonin gene-related peptide (CGRP). Relaxation was not attenuated by removal of the epithelium or by pretreatment of tissue with meclofenamate or the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine. Previous exposure of TSM to capsaicin did not eliminate the relaxation responses to subsequent capsaicin. Although...
Pelletier N, Robinson NE, Kaiser L, Derksen FJ.We investigated regional differences of in vitro responses of pulmonary arteries (6-mm OD) from the dorsocaudal (top) and cranioventral (bottom) lung regions to endothelium-dependent vasodilators (methacholine, bradykinin, and calcium ionophore A-23187). Methacholine relaxed endothelium-intact top vessels; however, in bottom vessels, a small relaxation preceded a profound contraction. In top vessels, removal of endothelial cells converted relaxation to contraction, and in bottom vessels it abolished relaxation and enhanced contraction. Bradykinin and A-23187 were more potent and caused greater...
Mills PC, Marlin DJ, Scott CM, Smith NC.The effect of nitric oxide synthase (NOS) inhibition during exercise on lactate production was investigated in five Thoroughbred horses. A standard exercise test (SET), consisting of three canters (approximately 55 per cent VO2max), with walking and trotting between each canter, was performed twice (control and test, in random order) by each horse. Nphi-nitro-L-arginine methyl ester (L-NAME; 20 mg kg-1), a competitive inhibitor of NOS, induced a significant increase (P < 0.05) in plasma lactate [5.7 (2.9) vs 11.8 (3.8) mmol L-1], which continued to increase despite administration of L-argin...
Rakestraw PC, Snyder JR, Woliner MJ, Sanders KM, Shuttleworth CW.To evaluate the role of nitric oxide (NO), vasoactive intestinal peptide (VIP), and a transmitter acting through an apamin-sensitive mechanism in mediating inhibitory transmission in the equine jejunal circular muscle, and to determine the distribution of VIP-and NO-producing nerve fibers in the myenteric plexus and circular muscle. Methods: Circular muscle strips were suspended in tissue baths containing an oxygenated modified Krebs solution and attached to isometric force transducers. Responses to electrical field stimulation (EFS), tetrodotoxin, the NO antagonists L-N-nitro-arginine-methyl-...
Marañón G, Manley W, Cayado P, García C, de la Muela MS, Vara E.Colic could be accompanied by changes in the morphology and physiology of organs and tissues, such as the intestine. This process might be, at least in part, due to the accumulation of oxidative damage induced by reactive oxygen (ROS) and reactive nitrogen species (RNS), secondary to intestinal ischemia. Glutathione (GSH), being the major intracellular thiol, provides protection against oxidative injury. The aim of this study was to investigate whether ischemia-induced intestinal injury could be related with alterations in GSH metabolism. Results: Ischemia induced a significant increase in lip...
Prieto D, Arcos LR, Martínez P, Benedito S, García-Sacristán A, Hernández M.The distribution of neuropeptide Y (NPY)-immunorective nerves and the receptors involved in the effects of NPY upon electrical field stimulation (EFS)- and noradrenaline (NA)-elicited contractions were investigated in horse penile small arteries. NPY-immunoreactive nerves were widely distributed in the erectile tissues with a particularly high density around penile intracavernous small arteries. In small arteries isolated from the proximal part of the corpora cavernosa, NPY (30 nM) produced a variable modest enhancement of the contractions elicited by both EFS and NA. At the same concentration...
Mills PC, Scott CM, Marlin DJ.We investigated the role of NO in the control of thermoregulation. We measured sweating rate and body temperatures (core, rectal and skin) in five thoroughbred horses during exercise of variable intensity on a high-speed treadmill. A standard exercise test (SET) consisting of three canters (8 m s-1), with walking and trotting between each canter, was performed twice, in random order, by each horse and N omega-nitro-L-arginine methyl ester (L-NAME; 20 mg ml-1), a competitive inhibitor of nitric oxide synthase (NOS), was infused into the central circulation after the first canter in the test SET...
