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.
Petrov R, MacDonald MH, Tesch AM, Benton HP.To investigate the effect of adenosine kinase inhibition on interleukin (IL)-1beta- and lipopolysaccharide (LPS)-induced cartilage damage. Methods: Articular cartilage was obtained from the metacarpophalangeal joints of 10 young adult horses. Following a stabilization period, weighed cartilage explants were exposed to IL-1beta (10 ng/ml) or LPS (50 microg/ml) to induce cartilage degradation. To test the potential protective effects of adenosine, these explants were simultaneously exposed to adenosine (100 microM), the adenosine kinase inhibitor 5'iodotubercidin (ITU, 1 microM) or to both adeno...
Benton HP, Esquivel AV, Rice AD, Giri SN.Pirfenidone is under investigation as an anti-inflammatory and anti-fibrotic agent in several organs including lung. Since important features of arthritic conditions include inflammation and long-term damage to articular cartilage, we have investigated whether PD can suppress chondrocyte responses to bacterial lipopolysaccharide (LPS) and interleukin 1 (IL-1); modulators that induce a cascade of inflammatory responses that lead to articular joint tissue damage. PD (0 - 5microM) showed no effect on cell number or viability when incubated with high density primary equine chondrocyte cultures for...
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...
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...
MacEachern KE, Smith GL, Nolan AM.Hypoxaemia accompanies dorsal recumbency in the horse and frequently complicates general anaesthesia. The physiology associated with this phenomenon is poorly understood. One possible cause of poor tolerance to dorsal recumbency is an absent or reduced response to hypoxic pulmonary vasoconstriction (HPV). This study compared the HPV response in isolated pulmonary artery vessels from equivalent regions of equine and bovine lung. Methods: Equine and bovine, in vitro study. Methods: Equine and bovine pulmonary arteries were removed from the lungs of euthanased horses and cattle. Measurements of i...
Hubert JD, Seahorn TL, Klei TR, Hosgood G, Horohov DW, Moore RM.The objective of this study was to determine the effect of infection with Strongylus vulgaris on serum cytokines and plasma nitric oxide (NO) concentrations in helminth-naive ponies. Group 1 (n = 21) was given 500 S. vulgaris L3 larvae and group 2 (n = 7) received a saline control. Ponies were monitored daily for clinical signs, and blood was collected for complete blood cell counts and serum cytokines (TNF, IL-1, IL-6) quantification. Group 1 ponies were depressed, anorexic, and febrile for variable periods of time. Plasma NO was increased on day 21 in group 1 and on days 9 and 21 in group 2....
Berhane Y, Bailey SR, Harris PA, Griffiths MJ, Elliott J.Elevated plasma homocysteine (HCy) concentration is a risk factor for cardiovascular diseases associated with endothelial dysfunction, including the human digital ischaemic disease, Raynaud's phenomenon. Objective: HCy causes dysfunction of equine vascular endothelium and elevated plasma concentrations predispose to laminitis. Objective: To determine 1) the concentration of HCy in vitro, which inhibits equine vascular endothelial cell function and 2) any association between risk of laminitis and plasma HCy concentration. Methods: Endothelial function was studied by measuring endothelium-depend...
Ha TY, Kim HS, Shin T.The expression of three isoforms of nitric oxide synthase (NOS) were examined in the testis and epididymis of a thoroughbred horse. Immunohistochemical studies demonstrated the presence of eNOS immunostaining in some germ cells in the seminiferous tubules and in vascular endothelial cells in the interstitial tissues. Interstitial cells, most likely Leydig cells, were also intensely immunopositive for eNOS. The pattern of immunostaining for nNOS was similar to that for eNOS in the testis. Weak expression of iNOS was detected in the seminiferous tubules of the testis, but intense expression was ...
Johnson A, Smith R, Saxne T, Hickery M, Heinegård D.Previous experiments have shown that addition of fragmented fibronectin can induce cartilage chondrolysis. In this study we investigated the fate of the collagen- and cell-binding molecules Cartilage oligomeric matrix protein (COMP) and chondroadherin. Methods: Equine articular cartilage explants were stimulated with the C-terminal and the N-terminal heparin-binding fragments of fibronectin respectively, and the conditioned media were analysed by both quantitative (ELISA) and qualitative (mass spectrometry, Western blots) methods. Results: Both COMP and chondroadherin were released in a dose-d...
Katz LM, Marr CM, Elliott J.Substance P (SP), a potent vasodilator, has been detected in equine digital sensory-motor nerves. The aim of the study was to characterise the functional responses of equine digital blood vessels to exogenous SP. Pre-constricted equine digital arteries (EDA) and veins (EDV) vasodilated in a biphasic, endothelium- and concentration-dependent manner to SP. A nitric oxide (NO) synthase inhibitor Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME; 300 microm) inhibited both phases of the relaxation response curve of EDAs to SP by >70%. In EDVs, the first relaxant phase to SP was largely...
Pinto CR, Paccamonti DL, Eilts BE, Venugopal CS, Short CR, Gentry LR, Thompson DL, Godke RA.In the present study, follicular fluids of estrous mares treated with saline solution (Control) or nitric oxide synthase (NOS) inhibitors were analyzed for nitric oxide (NO), estradiol-17beta (E2) and progesterone (P4) concentrations before and 36h after administration of human chorionic gonadotropin (hCG). Follicular fluids obtained before (0h) hCG administration from control mares had lower concentrations of NO than those obtained 36h after administration of hCG (58.3+/-17.8 micromol versus 340.4+/-57.7 micromol; P<0.05). A similar pattern was also noted for intrafollicular P4 in control ...
Janicke H, Taylor PM, Bryant CE.Equine endotoxaemia is an important cause of morbidity and mortality in horses caused by the interaction of bacterial lipopolysaccharide (LPS) with cells such as macrophages and vascular smooth muscle. In this study we isolated equine vascular smooth muscle from a variety of vessels and stimulated it with LPS and human interferon (hIFN)-gamma. Using reverse transcriptase polymerase chain reaction (rt-PCR) and Western blot analysis we show that cyclooxygenase-2 (COX-2) is readily expressed in equine vascular smooth muscle. Vascular smooth muscle cells produced prostaglandin E2 in response to LP...
Wiseman M, Henson F, Lee DA, Bader DL.Chondrocytes within articular cartilage respond to the mechanical stresses associated with normal joint loading via a series of signalling pathways. Specific biomolecules, such as nitric oxide (NO), have been implicated in these mechanotransduction processes. It has been shown that the synthesis of NO can be inhibited by dynamic compressive strain of chondrocytes in vitro which, in turn, leads to an up-regulation of specific metabolic parameters. Objective: Chondrocytes isolated from different joint locations and seeded in agarose constructs respond in a distinct manner to the application of d...
Mallem MY, Gogny M, Gautier F, Bucas V, Desfontis JC.To investigate the functional expression of beta3-adrenoceptors (beta3-ARs) in equine digital veins (EDVs) and to examine whether beta3-AR relaxation was altered in EDVs incubated with endotoxin. Methods: Forelimbs obtained from 30 horses. Methods: Forelimbs were obtained from horses in an abattoir. Equine digital veins were carefully removed from distal portions of the forelimbs. Rings of dissected EDVs were mounted in 5-mL organ baths to record isometric tension in the presence of various beta3-AR agonists (SR 58611A, ZD 2079, and ZM 215001). Results: In intact EDVs, isoprenaline, SR 58611A,...
Kim DY, Taylor HW, Moore RM, Paulsen DB, Cho DY.Osteoarthritis (OA) is the most common joint disease in horses. Chondrocyte apoptosis has been implicated as a major pathological OA change in humans and experimental animals but no studies have been performed on equine OA. Articular cartilage was collected from three normal and five OA horses. Histopathological changes were scored by a modified Mankin grading system. A terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was performed to identify chondrocyte apoptosis. Nitric oxide (NO) production from chondrocytes was indirectly evaluated by immunohistochemistr...
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...
Hubert JD, Seahorn TL, Klei TR, Hosgood G, Moore RM.The purpose of this study was to compare concentrations of nitric oxide (NO) in fresh plasma versus frozen plasma, and determine the temporal effects of freezing on jugular venous plasma NO concentrations in clinically healthy ponies. Twenty-eight helminth-naive ponies, aged from 4 to 6 mo, were raised and maintained under parasite-free conditions. Blood was collected from the jugular vein, centrifuged, and the plasma supernatant was analyzed fresh for NO concentrations using a chemiluminescent method. The remaining samples were aliquoted into 12 samples and stored at -70 degrees C until they ...
de la Calle J, Burba DJ, Ramaswamy CM, Hosgood G, Williams J, LeBlanc C, Moore RM.To compare plasma and synovial fluid endothelin-1 (ET-1) and nitric oxide (NO) concentrations in clinically normal horses and horses with joint disease. Methods: 36 horses with joint disease, and 15 horses without joint disease. Methods: Horses with joint disease were assigned to 1 of the 3 groups (ie, synovitis, degenerative joint disease [DJD], or joint sepsis groups) on the basis of findings on clinical and radiographic examination and synovial fluid analysis. Endothelin-1 and NO concentrations were measured in plasma from blood samples, collected from the jugular vein and ipsilateral cepha...
Tesch AM, MacDonald MH, Kollias-Baker C, Benton HP.To investigate accumulation of extracellular adenosine (ADO) by equine articular chondrocytes and to compare effects of adenosine kinase inhibition and adenosine deaminase inhibition on the amount of nitric oxide (NO) produced by lipopolysaccharide (LPS)-stimulated chondrocytes. Methods: Articular cartilage from metacarpophalangeal and metatarsophalangeal joints of 14 horses. Methods: Chondrocytes were cultured as monolayers, and cells were incubated with LPS, the adenosine kinase inhibitor 5'-iodotubercidin (ITU), or the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine hydro...
Orth MW, Peters TL, Hawkins JN.Glucosamine and chondroitin sulphate in many animal and human trials has improved joint health. In vitro studies are beginning to clarify their mode of action. The objective of this research was to: 1) determine at what concentrations glucosamine-HCl (GLN) and/or chondroitin sulphate (CS) would inhibit the cytokine-induced catabolic response in equine articular cartilage explants and 2) to determine if a combination of the 2 was more effective at inhibiting the catabolic response than the individual compounds. Articular cartilage was obtained from carpal joints of horses (age 1-4 years). Carti...
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...
van Hoogmoed LM, Harmon FA, Stanley S, White J, Snyder J.The objective of this study was to determine if a correlation exists between the presence of nitric oxide and prostaglandin release in the equine ventral colon smooth muscle, since this relationship may accentuate the inflammatory process during intestinal injury. Tissue was collected from the ventral colon, cut into muscle strips oriented along the circular, longitudinal and taenial layers, and mounted in a tissue bath system. Samples of the bath fluid were collected before, following electrical field stimulation (EFS), and following EFS in the presence of L-NAME, a nitric oxide synthase inhi...
Pinto CR, Paccamonti DL, Eilts BE, Short CR, Godke RA.Recent studies suggest that nitric oxide (NO) may have a role in regulating ovarian physiology. To investigate the role of NO during ovulation in mares, inhibitors of the nitric oxide synthase (NOS) were administered to estrous mares. Forty cycling mares (20 horses and 20 pony mares) were allotted to one of the three treatment groups. Once a follicle was at least 27 mm in diameter, but smaller than 35 mm, mares were given one of the following treatments: saline solution 0.9% (n = 20, w/v, i.v., every 12 h), Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME; n = 10, 148 micromol/kg, i....
Kindig CA, McDonough P, Erickson HH, Poole DC.Within the moderate exercise intensity domain, the speed of oxygen uptake (V(O(2))) kinetics at the transition to a higher metabolic rate is thought to be limited by an inertia of the oxidative machinery. Nitric oxide (NO)-induced inhibition of O(2) consumption within the electron transport chain may contribute to this inertia. This investigation tested the hypothesis that a reduction or removal of any such NO effect via infusion of N(omega)-nitro-L-arginine methyl ester (L-NAME; a NOS inhibitor) would speed V(O(2)) kinetics at the onset of moderate exercise. Five Thoroughbred geldings underwe...
Hammond RA, Flower RJ, Bryant CE.THE gene encoding equine inducible nitric oxide synthase (iNOS) was cloned and sequenced. The strategy consisted of the amplification by PCR of message isolated from primary cultures of equine articular chondrocytes (Frean et al 1997) treated with 100 mg mlÿ1 LPS (Escherichia coli serotype O127:B8). PCR primer pairs were generated by comparison of cross-species published iNOS nucleotide sequences. The sequences of the 30 and 50 termini were derived by the generation of PCR products spanning those regions. The assembly of sequenced PCR fragments revealed a 3930 complete nucleotide sequence wit...
Heinonen E, Nyman G, Meriläinen P, Högman M.Dependent atelectatic lung areas open towards the end of inspiration when the lung opening pressure increases, and recollapse during expiration. We hypothesized that inhaled nitric oxide (NO) counteracts hypoxic vasoconstriction in these collapsing lung areas, resulting in increased pulmonary shunt perfusion. Methods: We administered NO as a pulse and varied the pulse timing during inspiration in equine anaesthesia, where atelectasis develops regularly. Six spontaneously breathing standard breed trotters were studied under isoflurane anaesthesia in lateral recumbency. NO pulsed into the first ...
Njoku CJ, Saville WJ, Reed SM, Oglesbee MJ, Rajala-Schultz PJ, Stich RW.Equine protozoal myeloencephalitis (EPM) is a disease of horses that is primarily associated with infection with the apicomplexan Sarcocystis neurona. Infection with this parasite alone is not sufficient to induce the disease, and the mechanism of neuropathogenesis associated with EPM has not been reported. Nitric oxide (NO) functions as a neurotransmitter, a vasodilator, and an immune effector and is produced in response to several parasitic protozoa. The purpose of this work was to determine if the concentration of NO metabolites (NO(x)(-)) in the cerebrospinal fluid (CSF) is correlated with...
Benton HP, MacDonald MH, Tesch AM.To determine whether adenosine influences the in vitro release of nitric oxide (NO) from differentiated primary equine articular chondrocytes. Methods: Articular cartilage harvested from the metacarpophalangeal and metatarsophalangeal joints of 11 horses (3 to 11 years old) without history or clinical signs of joint disease. Methods: Chondrocytes were isolated, plated at a high density (10(5) cells/well), and treated with adenosine, the adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA), bradykinin, or other agents that modify secondary messenger pathways alone or in combination ...
Tung JT, Venta PJ, Caron JP.To determine the effects of recombinant equine IL-1beta and a number of antiinflammatory compounds on the expression and activity of inducible nitric oxide synthase (iNOS) in cultured equine chondrocytes. Methods: RT-PCR methods were used to amplify a portion of the equine iNOS message to prepare an RNA probe. Northern blot analysis was used to quantify the expression of iNOS in first passage cultures of equine articular chondrocytes propagated in the presence or absence of recombinant equine interleukin-1beta (reIL-1beta), dexamethasone (DEX), polysulfated glycosaminoglycan (PSGAG), hyalurona...
Malone ED, Kannan MS.To determine whether intestinal ischemia would alter activity of the jejunum in vitro or alter staining characteristics for certain types of enteric neurotransmitters. Methods: Jejunal samples obtained from 10 ponies. Methods: Jejunal samples were obtained from locations proximal and distal to an area of small intestine made ischemic for 60 minutes. A portion of each sample was stained to detect substance P-like immunoreactivity, cholinergic and adrenergic neurons, and nitric oxide synthase. Portions of the remaining samples were suspended in muscle baths. General activity patterns (frequency ...
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...
Menzies-Gow NJ, Bailey SR, Berhane Y, Brooks AC, Elliott J.To determine the effect of endotoxin (lipopolysaccharide [LPS]) on vasoactive mediator production by cultured equine digital vein endothelial cells (EDVECs). Methods: EDVECs obtained from forelimb digital veins of 7 healthy adult horses. Methods: EDVECs were incubated with or without LPS (1 microg/mL) for 0, 2, 4, 6, 22, and 24 hours. The EDVECs were incubated for 18 hours with LPS (10 pg/mL to 1 microg/mL) with or without ibuprofen, cycloheximide, or L-nitroarginine methyl ester. Medium concentrations of prostacyclin, cyclic guanosine monophosphate, endothelin-1, and thromboxane A(2) were det...
Michalska J, Nowicka B, Wessely-Szponder J.We hypothesized that in horses with naturally occurring joint disorders, the neutrophil response, acute phase response (APR), and oxidative stress parameters elevated significantly and are markers of increased inflammatory response in these conditions. Therefore, the first aim of the study was to evaluate neutrophil response, oxidative status, and APR. The neutrophil activity was assessed on the basis of elastase, myeloperoxidase (MPO), and alkaline phosphatase release, whereas free radical generation was assessed on the basis of nitric oxide and superoxide production. Acute phase response was...
Heinonen E, Nyman G, Meriläinen P, Högman M.Dependent atelectatic lung areas open towards the end of inspiration when the lung opening pressure increases, and recollapse during expiration. We hypothesized that inhaled nitric oxide (NO) counteracts hypoxic vasoconstriction in these collapsing lung areas, resulting in increased pulmonary shunt perfusion. Methods: We administered NO as a pulse and varied the pulse timing during inspiration in equine anaesthesia, where atelectasis develops regularly. Six spontaneously breathing standard breed trotters were studied under isoflurane anaesthesia in lateral recumbency. NO pulsed into the first ...
Hunter RP, Short CR, McClure JR, Koch CE, Keowen ML, VanSteenhouse JL, Dees AA.Cimetidine (CIM) is an H2-receptor antagonist that has been used in racehorses in an attempt to reduce the occurrence of stress-related gastric ulceration. It has also been shown to produce several useful effects other than its gastric acid suppression properties. Further, it is a well documented antagonist of cytochrome P-450 (CYP) mediated oxygenation reactions. Nitric oxide (NO), a recently discovered mediator or modifier of numerous physiological functions, is generated by several forms of nitric oxide synthase (NOS), one of which is inducible (iNOS). Inducible NOS, expressed in neutrophil...
Martínez AC, Prieto D, Hernández M, Rivera L, Recio P, García-Sacristán A, Benedito S.This study evaluates the mechanisms underlying endothelium-dependent responses to acetylcholine in horse deep dorsal penile veins. Acetylcholine-induced relaxation was abolished by endothelium removal, the soluble guanylyl cyclase-inhibitor, and the nitric oxide (NO) synthase inhibitors. Acetylcholine-induced relaxation was inhibited by high K+ concentrations and blockade of large-conductance Ca(2+)-activated potassium (BK(Ca)) channels, and voltage-dependent potassium (K(v)) channels. Relaxations were unaffected by a small-conductance K(Ca) (SK(Ca)) channel blocker, or an ATP-sensitive potass...
Costa LR, Seahorn TL, Moore RM, Oliver JL, Hosgood GL.To determine concentrations of nitric oxide (NO) in plasma and bronchoalveolar lavage fluid (BALF) and localize nitric oxide synthesis in the lungs of horses with summer pasture-associated obstructive pulmonary disease (SPAOPD). Methods: 7 adult horses with SPAOPD and 6 clinically normal adult horses. Methods: Severity of SPAOPD was determined by use of clinical scores, change in intrapleural pressure (APpl) during tidal breathing, cytologic analysis of BALF, and histologic evaluation of lung specimens obtained during necropsy. Nitric oxide concentrations in plasma, BALF and epithelial lining ...
Miyamoto A, Kanda J, Nishio A.Transmural nerve stimulation (TNS) induced relaxations in porcine and bovine basilar arteries which were abolished by tetrodotoxin (TTX) and by L-nitro-arginine (LNAG). However, TNS induced contractions in equine basilar artery which were abolished by TTX and by guanethidine, but not by LNAG. These results suggest that the TNS-induced contractions of equine basilar arteries may be mediated by norepinephrine release.
Young LE, Marlin DJ, McMurphy RM, Walsh K, Dixon PM.Inhaled nitric oxide, a selective pulmonary vasodilator, is known to improve arterial oxygenation after cardiopulmonary bypass and during acute respiratory distress syndrome in humans. During general anaesthesia with spontaneous ventilation, healthy adult horses develop large alveolar-arterial oxygen tension differences. In this study, we have determined the effects of inhaled nitric oxide (10 parts per million (ppm)) on venous admixture and pulmonary haemodynamics in horses anaesthetized with halothane. Seven adult horses were studied twice in random sequence. After premedication with romifid...
Frean SP, Bryant CE, Fröling IL, Elliott J, Lees P.Recent research in several species has suggested nitric oxide (NO) as a mediator of articular cartilage damage and an inhibitor of cartilage matrix neosynthesis. This study investigated NO production by cultured equine articular chondrocytes in response to 2 arthritogenic molecules, namely lipopolysaccharide (LPS) and interleukin-1 beta (IL-1 beta), and compared NO production by cultured equine synoviocytes stimulated with LPS. Synoviocytes exhibited a low basal level of NO synthesis (measured as nitrite, a NO metabolite) that was neither significantly increased nor decreased by exposure to LP...
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...
van Hoogmoed LM, Harmon FA, Stanley S, White J, Snyder J.The objective of this study was to determine if a correlation exists between the presence of nitric oxide and prostaglandin release in the equine ventral colon smooth muscle, since this relationship may accentuate the inflammatory process during intestinal injury. Tissue was collected from the ventral colon, cut into muscle strips oriented along the circular, longitudinal and taenial layers, and mounted in a tissue bath system. Samples of the bath fluid were collected before, following electrical field stimulation (EFS), and following EFS in the presence of L-NAME, a nitric oxide synthase inhi...
Chen Q, Tong Q, Ge H, Li W, Liu J, Wang Y, Guo Z, Quan F, Zhang Y.SP110 has previously shown to be a genetic determinant of host resistance to the intracellular pathogen infection in mouse and human. However, its relevant biological information in large non-primate animals still remains unknown. Here we report the novel discovery and characterization of three transcript variants of horse SP110. The transcript variant 1 (Tv1) of horse SP110 with the longest open reading frame has four domains (Sp100, SAND, PHD and Bromo domain). Tv2 and Tv3 share the same N-terminal sequence as Tv1, which contains Sp100 and SAND. We show that Tv2 is generated from alternative...
Yu M, Wang Z, Robinson NE, Leblanc PH.The distribution of inhibitory nerves and the mediator of the inhibitory nonadrenergic noncholinergic (iN-ANC) nervous system were investigated in smooth muscle preparations from seven regions of equine airways. In tissues incubated with atropine and precontracted with histamine, electrical field stimulation produced frequency-dependent relaxation, and the magnitude of the relaxation decreased from trachea to central bronchi and was absent in peripheral airways. The degree of relaxation in bronchi was not simply a function of bronchial size or generation. Propranolol inhibited part of the rela...
Pinto CR, Paccamonti DL, Eilts BE, Short CR, Godke RA.Recent studies suggest that nitric oxide (NO) may have a role in regulating ovarian physiology. To investigate the role of NO during ovulation in mares, inhibitors of the nitric oxide synthase (NOS) were administered to estrous mares. Forty cycling mares (20 horses and 20 pony mares) were allotted to one of the three treatment groups. Once a follicle was at least 27 mm in diameter, but smaller than 35 mm, mares were given one of the following treatments: saline solution 0.9% (n = 20, w/v, i.v., every 12 h), Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME; n = 10, 148 micromol/kg, i....
Hanafusa Y, Cho KO, Kanemaru T, Wada R, Sugimoto C, Onuma M.The present study was designed to investigate the role of cytokines in the pathogenesis of Babesia caballi in experimentally infected horses. The expression of cytokine mRNA was determined by using reverse transcription-polymerase chain reaction in two B. caballi-infected horses for 2 weeks after the infection. In one horse, there was up-regulation of interferon-gamma, tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 mRNAs, while in the second horse, expression of only TNF-alpha mRNA was up-regulated. No change was observed in interleukin-4 mRNA in both of the horses. To know the rela...
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...
Venugopalan CS, Moore RM, Holmes EP, Sedrish SA, Koch CE.1. The role of endothelium in modulating equine colonic vessel responses to histamine (HST), 5-hydroxytryptamine (5-HT), bradykinin (BK) and acetylcholine (ACh) was evaluated in vitro. 2. Segments of mesenteric arteries and veins were collected from the left ventral colon of six adult horses destined for euthanasia for reasons unrelated to cardiovascular or gastrointestinal systems. Vessels were gently cleansed and cut into 4 mm wide rings. 3. Three vessel conditions namely endothelium intact, endothelium removed and N omega-nitro-L-arginine methyl ester (L-NAME)-treated were used for both art...
Berhane Y, Elliott J, Bailey SR.Haemodynamic disturbances leading to ischaemia and reperfusion injury of the digit are thought to be involved in the pathophysiology of acute equine laminitis. Identification of physiological regulators of blood flow through the equine digit is important in identifying factors, which may predispose animals to laminitis. A method was developed to assess endothelium-dependent responses of the isolated Krebs-perfused equine digit by co-administration of 5-hydroxytryptamine (5-HT) with vasodilator agents, carbachol (CCh), bradykinin (BK) and substance P (SP). Bolus co-administration of CCh (0.02-2...
MacNicol JL, Pearson W. organ culture can provide insight into isolated mucosal responses to particular environmental stimuli. The objective of the present study was to investigate the impact of a prolonged culturing time as well as the addition of acidic gastric fluid into the environment of cultured gastric antral tissue to evaluate how altering the commonly used neutral environment impacted tissue. Furthermore, we aimed to investigate the impact of G's Formula, a dietary supplement for horses, on the secretion of gastrin, interleukin1-beta (IL-1β), and nitric oxide (NO). These biomarkers are of interest due to ...
Pinto CR, Paccamonti DL, Eilts BE, Venugopal CS, Short CR, Gentry LR, Thompson DL, Godke RA.In the present study, follicular fluids of estrous mares treated with saline solution (Control) or nitric oxide synthase (NOS) inhibitors were analyzed for nitric oxide (NO), estradiol-17beta (E2) and progesterone (P4) concentrations before and 36h after administration of human chorionic gonadotropin (hCG). Follicular fluids obtained before (0h) hCG administration from control mares had lower concentrations of NO than those obtained 36h after administration of hCG (58.3+/-17.8 micromol versus 340.4+/-57.7 micromol; P<0.05). A similar pattern was also noted for intrafollicular P4 in control ...
Bailey SR, Elliott J.Endotoxin has been implicated in the pathophysiology of acute laminitis. The aim of this study was to examine the direct effects of endotoxin on isolated equine digital blood vessels. Equine digital veins (EDV), incubated in Krebs-Henseleit solution containing lipopolysaccharide (LPS) (1 microg/ml) became hyporesponsive to 5-HT after 16 h. Cycloheximide and ibuprofen blocked this effect of LPS and increased the maximum response obtained to 5-HT when compared to control vessels. L-nitroarginine methyl ester (L-NAME) reversed the hyporesponsiveness caused by LPS. Vessels maintained in culture me...
Venugopalan CS, Moore RM, Holmes EP, Sedrish SA.To determine the in vitro contractile responses of equine colonic arteries to angiotensin II, histamine, serotonin, norepinephrine, prostaglandin F2 alpha, vasopressin, and a thromboxane-B2-analogue. Methods: The tension generated in colonic arterial rings placed in organ baths with oxygenated Tyrode's solution at 37 degrees C after exposure to the previously mentioned chemical agents was measured using force-transducers interfaced with a polygraph. Methods: Large colon arterial rings collected from eight horses. Methods: The rings were allowed to equilibrate for 45 minutes after applying 2 g ...
Benton HP, Esquivel AV, Rice AD, Giri SN.Pirfenidone is under investigation as an anti-inflammatory and anti-fibrotic agent in several organs including lung. Since important features of arthritic conditions include inflammation and long-term damage to articular cartilage, we have investigated whether PD can suppress chondrocyte responses to bacterial lipopolysaccharide (LPS) and interleukin 1 (IL-1); modulators that induce a cascade of inflammatory responses that lead to articular joint tissue damage. PD (0 - 5microM) showed no effect on cell number or viability when incubated with high density primary equine chondrocyte cultures for...
Welter H, Bollwein H, Weber F, Rohr S, Einspanier R.The expression of the endothelial and inducible nitric oxide synthases (eNOS and iNOS, respectively) was examined in the endometrium of cyclic and pregnant mares by real-time polymerase chain reaction and immunohistology. The concentration of eNOS mRNA varied throughout the oestrous cycle, with significantly higher transcripts on Day 5 of the oestrous cycle (P 0.05). In early pregnant mares both eNOS and iNOS mRNA increased between Days 12 and 15 (P < 0.05). In cyclic mares, eNOS protein was detected immunocytochemically in endometrial epithelia, the basement membrane, the endothelial laye...
Bird JL, May S, Bayliss MT.Arthroses are debilitating diseases of articular joints which result in erosion of the cartilage extracellular matrix. Nitric oxide (NO) is a major component of the inflammatory response, and has been implicated as a mediator of some of the effects of the proinflammatory cytokine, interleukin-1 (IL-1). In this study, we investigated the role of NO in the regulation of proteoglycan degradation in equine articular cartilage. NO fully mediated the suppressive effect of IL-1 on proteoglycan synthesis. However, NO was also antagonistic to proteoglycan degradation, irrespective of whether degradatio...
Nogueira BCF, Orozco AMO, Argumedo AK, de Oliveira Faustino A, de Oliveira LL, da Fonseca LA, Campos AK.Ticks have saliva rich in immunoregulatory molecules that interfere with the host's physiology in order to feed. This study aimed to evaluate the concentration of acute phase proteins and circulating oxidative stress in response to infestation by Amblyomma sculptum and Dermacentor nitens in two breed horses, Mangalarga Marchador and Breton Postier, to define resistance or susceptibility to ticks. Among the oxidative stress markers, we observed lower malondialdehyde and nitric oxide in horses with tick infestation, consequently not altering the antioxidant enzymes. Breton Postier with tick infe...
Alves NC, Diniz SA, Viegas RN, Cortes SF, Costa ED, Freitas MM, Martins-Filho OA, Araújo MSS, Lana ÂMQ, Wenceslau RR, Lagares MA.The aim of this study was to improve the quality of frozen-thawed equine sperm by the addition of caffeine to it. Semen from nine stallions was frozen and different concentrations of caffeine (3, 5 and 7.5 mM) were added to frozen-thawed semen. The sperm kinetic parameters, membrane functionality and integrity, and acrosome integrity and spontaneous acrosome reacted sperm were evaluated with a computer-assisted sperm analysis, a hypoosmotic swelling test and epifluorescent microscopy, respectively. Nitrite and hydroperoxide concentrations of frozen-thawed semen were measured using spectrophot...
Berhane Y, Bailey SR, Putignano C, Elliott J.The role of endothelium-derived relaxing factors was studied in the regulation of vascular responses in the Krebs perfused equine isolated digit. Perfusion pressure was recorded in response to bolus doses of 5-hydroxytryptamine (6 nmol) alone or co-administered with carbachol (CCh; 0.2 micromol), bradykinin (BK; 0.2 nmol), substance P (SP; 0.2 nmol) or sodium nitroprusside (SNP; 0.2 micromol). N(omega)-Nitro-L-Arginine methyl ester hydrochloride (L-NAME; 300 microm) caused partial but significant inhibition of CCh-induced vasodilatory response, whereas BK and SP-induced responses were resistan...
Keen JA, Hillier C, McGorum BC, Nally JE.Endothelin-1 (ET-1) may be a key mediator in the pathogenesis of laminitis, but endothelin-mediated responses in the venous microcirculation of the equine foot have yet to be fully characterised. Objective: To characterise the response of equine laminar veins to ET-1 and evaluate the ET-1 receptor subtypes that mediate this response. Methods: Small veins (150-500 microns) draining the equine digital laminae from healthy horses and ponies subjected to euthanasia at an abattoir were investigated using wire myography. Concentration response curves were constructed for ET-1 in the presence of ETA ...
