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.
Manohar M.Strenuously exercising Thoroughbreds exhibit a dramatic increase in pulmonary capillary blood pressure, which contributes to stress failure of pulmonary capillaries resulting in exercise induced pulmonary haemorrhage (EIPH). One strategy to prevent EIPH is, therefore, to lower the pulmonary capillary blood pressure of exercising horses. Recent work in several species suggests that nitric oxide plays a significant role in maintaining low vascular resistance in the pulmonary circulation; however, the effects of nitrovasodilators (which work via the same mechanism as nitric oxide) on equine pulmo...
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.
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...
Elliott J, Bryant CE, Soydan J.Isolated equine digital veins were examined in vitro to study the importance of the endothelium in the responses to both vasodilator and vasoconstrictor agents and to characterise the endothelial-derived mediators involved. Carbachol (Cch; 1 microM) and bradykinin (Bk; 1 nM) caused relaxation of U44069-induced tone by 79.5 +/- 0.35% and 73.7 +/- 4.0% respectively. Mechanical removal of the endothelium completely prevented relaxant responses to Cch and to Bk showing they were mediated by the endothelium. Treatment of veins with NG-nitro-L-arginine methyl ester (L-NAME; 30 and 300 microM) inhibi...
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...
Prieto D, Simonsen U, Martín J, Hernández M, Rivera L, Lema L, García P, García-Sacristán A.The distribution of acetylcholinesterase (AChE)-positive nerve fibers and cells, as well as the effects of acetylcholine (ACh) on ureteral smooth muscle and small resistance arteries were investigated in the equine ureter by means of histochemical, classic organ baths and myograph techniques. AChE-positive nerve fibers were widely distributed throughout the ureteral wall forming muscular, subepithelial and perivascular nerve plexuses, whose density was highest at the intravesical ureter. AChE-positive nerve cells were also identified grouped as adventitial or intramural ganglia. ACh increased ...
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...
Ascenzi P, Coletta M, Desideri A, Polizio F, Condò SG, Giardina B.The effect of inositol hexakisphosphate (IHP) on the spectroscopic (EPR and absorbance) properties of the nitric oxide derivative of ferrous horse and bovine hemoglobin (Hb) has been investigated. In the absence of IHP, the nitric oxide derivative of ferrous horse Hb shows spectroscopic properties similar to those of the corresponding derivative of ferrous human Hb that are generally taken as typical of the high affinity state of tetrametric hemoproteins. Similar to human Hb, the addition of IHP to the nitric oxide derivative of ferrous horse Hb induces a transition toward a species characteri...
Steffey EP, Johnson BH, Eger EI, Howland D.Breathing 79% nitrous oxide (N2O) in oxygen increased the rate of accumulation of bowel gas during intraluminal bowel segment infusions of hydrogen, methane (CH4), air, or carbon dioxide (CO2) in four pentobarbital-anesthetized dogs more than did breathing 100% oxygen. A N2O-associated increase in the volume of naturally produced intestinal gas in five halothane-anesthetized ponies corroborated the findings in the dog studies. In a second group of four dogs a bolus of CH4 or CO2 was injected into the bowel lumen. When the dogs breathed O2 the bowel gas volume decreased. Gas was virtually absen...
Schneider NR, Yeary RA.Elimination kinetics of nitrite and nitrate in the dog, sheep, and pony were determined. The elimination half-lives of nitrite were 0.499, 0.475, and 0.566 hours in the dog, sheep, and pony, respectively; those of nitrate were 44.681, 4.233, and 4.821 hours. Apparent specific volumes of distribution (V'd) of nitrite were variable among the 3 species--1,623.7 ml/kg in the dog, 278.0 ml/kg in the sheep, and 191.6 ml/kg in the pony. The V'd of nitrate were less varied--dog, 238.5 ml/kg; sheep, 291.1 ml/kg; and pony, 209.3 ml/kg. In the in vitro studies on protein binding in canine plasma, the ext...
Manohar M, Goetz TE, Hassan AS, Rothenbaum P, Humphrey S.The present study was carried out to determine whether inhibition of nitric oxide (NO) synthase promotes anaerobic metabolism in exercising horses, resulting in a significantly increased blood lactate concentration. N(omega)-nitro-L-arginine methyl ester (L-NAME) is a potent inhibitor of NO synthase that has been tested in horses and other species. Two sets of experiments, namely placebo (saline control) and L-NAME (20 mg/kg, i.v.) studies, were carried out on seven healthy, sound, exercise-trained, Thoroughbred horses in random order, 6 to 7 days apart. In both experiments, an incremental exe...
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...
Gilhooly MH, Eades SC, Stokes AM, Moore RM.To measure and compare palmar digital venous plasma nitric oxide (NO) concentrations and digital arterial blood flow after application of topical nitroglycerine (NTG). Methods: Experimental study. Methods: Healthy adult horses (n=8). Methods: Digital blood flow was measured by an ultrasonic Doppler flow probe surgically implanted around the medial palmar digital artery. Blood was collected from a catheter placed in the medial palmar digital vein for quantification of NO. NTG patches, NTG ointment or control patches were placed over the palmar digital vessels at the level of the fetlock. Two ho...
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...
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...
Auckburally A, Wiklund M, Lord P, Nyman G.To measure changes in regional lung perfusion using CT angiography in mechanically ventilated, anesthetized ponies administered pulsed inhaled nitric oxide (PiNO) during hypotension and normotension. Methods: 6 ponies for anesthetic 1 and 5 ponies for anesthetic 2. Methods: Ponies were anesthetized on 2 separate occasions, mechanically ventilated, and placed in dorsal recumbency within the CT gantry. Pulmonary arterial, right atrial, and facial arterial catheters were placed. During both anesthetics, PiNO was delivered for 60 minutes and then discontinued. Anesthetic 1: hypotension (mean arter...
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 ...
Heinonen E, Hedenstierna G, Meriläinen P, Högman M, Nyman G.To study the effect of the pulsed delivery of nitric oxide (NO) on pulmonary gas exchange in the anaesthetized horses. Design Prospective, controlled randomized. Methods: Five healthy Standardbred trotters, three geldings and two mares. Methods: The horses were anaesthetized with thiopentone and isoflurane and positioned in dorsal recumbency. Nitric oxide was added as a pulse to the inspired gas during the first half of each inspiration. In three horses the effect of NO on the ventilation-perfusion distribution was also investigated using the multiple inert gas elimination technique. Data w...
Alkhadrawy JMH, Aboelmaaty AM, Abou-Ahmed MM, Ghallab AM.Commercial embryo flushing of horses has required hormonal management of both the donor and recipient mares throughout the breeding season. Unassigned: This study aimed to find out the effect of using human chorionic gonadotropin (hCG) and prostaglandin F2α (PG) on the ovarian and uterine dynamics and hemodynamics, estradiol (E2), progesterone, oxidants-antioxidants, and blood biochemicals in embryo donor mares during the hottest months of the year in a subtropical climate. Unassigned: Three Control estrous cycles of native mares (10-20 years; = 10) followed by two treated cycles with hCG an...
Busch F, Leal ODA, Siebers N, Brüggemann N.During composting of organic waste, nitrogen is lost through gaseous forms and ion leaching. Biochar has been shown to capture mineral nitrogen (N: NH and NO ) from compost, which we hypothesize reduces NO formation. However, associating N captured by biochar with the dynamics of NO and other greenhouse gas (GHG) emissions during composting remains unstudied and was the aim of this work. We composted (outdoor for 148 days) together kitchen scraps (43.3% dw, where dw is dry weight), horse manure (40.9% dw), and wheat (Triticum aestivum L) straw (15.8% dw) without (Control) or with biochar (Bc,...
Aboelmaaty AM, Elgharieb AEA, El-Debaky HA, Alkhadrawy JMH, Abou-Ahmed MM, Ghallab AM.Senility influences fertility in women and companion animals, especially horses. Unassigned: This study aimed to investigate the effect of aging in horses on the daily changes in the dominant follicle (DF) dynamics and hemodynamics, antimüllerian hormone (AMH), enzymes, antioxidants, and ovarian hormones during the estrous cycle. Unassigned: Ovaries of old mares ( = 5, age >20 years) and young native mares ( = 6, age <10 years) were scanned during 6 different estrous cycles from March 2022 to August 2023 with Doppler ultrasound. The DF diameter and color area, the corpus luteum (CL) dia...
Abdelnaby EA, ElKader NAA, Yehia SG, Salem NY, Ramadan ES, Khattab MS, Farghali HA, Emam IA.This study aimed to demonstrate the vaginal tissue alterations via vaginal biopsy and hemodynamic alterations by introducing chromoendoscopy to analyse the effect of equine vaginitis on the oxidative and hormonal profile. Mares were divided into normal mares (N = 10) and affected mares (N = 10). Animals were subjected to Doppler ultrasonographic evaluation, endoscopic examination, oxidative stress was estimated, and biopsy samples were taken for histopathology and immunohistochemistry. Uterine body (UB) thickness (mm), circumference (mm) and area (mm) elevated significantly in infected...
Leo LK, Bergvall KE.Equine aural plaque caused by equine papilloma viruses is common worldwide and affected horses can show severe clinical signs. Due to its viral aetiology, in some countries affected horses are not allowed to compete. Since lesions persist, showing no spontaneous regression, effective and safe treatment is required. Currently, the only treatment with consistent efficacy is imiquimod. Treatment time is prolonged and adverse effects are common. In humans, papilloma warts are successfully and safely treated with topical nitric-zinc complex solutions inducing a painless caustic effect. Objective: T...
Mirzaei A, Hajimohammadi A.Sixty-one horses were included in this study and classified into three groups based on the severity of colic, assessed by heart rate, oral mucous membrane color, and abdominal distension. The groups consisted of a strangulating colic (SC) group (n=21), a non-strangulating colic (NC) group (n=20), and a control group (n=20) of randomly selected healthy horses without colic. Serum concentrations of tumor necrosis factor α (TNFα), haptoglobin (Hp), nitric oxide (NO), malondialdehyde (MDA), zinc, iron, and copper were measured in all horses. Receiver operating characteristic (ROC) analysis was c...
Meeremans M, Devriendt B, Bairiot S, Van Poucke M, Peelman L, Demeyere K, Meyer E, Van Vlierberghe S, De Schauwer C.Macrophages play key roles in tissue homeostasis and regeneration-associated inflammation. Unlike humans, a reliable protocol to obtain and polarise equine monocyte-derived macrophages is lacking. In this study the polarisation of equine macrophages, derived from CD172a peripheral blood monocytes is described. After differentiation, IFN-γ/LPS or IL-4 were used to induce pro- and anti-inflammatory phenotypes, respectively. Evaluation criteria included morphology, mRNA (RT-qPCR) and protein expression (flow cytometry, immunofluorescence), nitric oxide and arginase production, cytokine secretion...
