The endothelium in horses is a thin layer of cells lining the interior surface of blood vessels, playing a significant role in vascular function and homeostasis. It is involved in the regulation of blood flow, coagulation, and immune response. The endothelium also facilitates the exchange of substances between the bloodstream and surrounding tissues. In horses, endothelial function can be affected by various factors, including inflammation, metabolic disorders, and infectious diseases. Understanding the behavior and pathology of the endothelium is essential for comprehending equine cardiovascular health and disease mechanisms. This page gathers peer-reviewed research studies and scholarly articles that explore the structure, function, and pathological changes of the endothelium in horses.
Ledbetter EC, Scarlett JM.To describe morphologic features, pachymetry and endothelial cell density of the normal equine cornea and limbus by in vivo confocal microscopy. Methods: Ten horses without ocular disease. Methods: The central and peripheral corneas were examined with a modified Heidelberg Retina Tomograph II and Rostock Cornea Module using a combination of automated and manual image acquisition modes. Thickness measurements of various corneal layers were performed and endothelial cell density determined. Results: Images of the constituent cellular and noncellular elements of the corneal epithelium, stroma, en...
Zerpa H, Berhane Y, Elliott J, Bailey SR.Cooling-enhanced contractile responses in cutaneous arteries have been reported to involve the activation of alpha(2C)-adrenoceptors, but their role in cutaneous veins is not clearly understood. The aim was to pharmacologically characterize the subtype of postsynaptic alpha(2)-adrenoceptors in the equine digital vein mediating contraction at two temperatures. The increase in isometric tension of endothelium-denuded equine digital vein in response to UK-14304 was studied in the absence and presence of relatively selective alpha(2)-adrenoceptor antagonists at temperatures of either 30 degrees C ...
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...
Huang H, Lavoie-Lamoureux A, Lavoie JP.The endothelium plays a critical role in regulating leukocyte recruitment and migration during inflammation. Recent studies provide evidence that acetylcholine (ACh) and other cholinergic mediators block endothelial cells activation and leukocyte recruitment during inflammation. We thus postulated that the non-neuronal cholinergic system might modulate the recruitment of neutrophils during allergic pulmonary inflammation. In the present study, we examined the effects of cholinergic stimulation on the expression of neutrophil chemokines and adhesion molecules by endothelial cells stimulated by ...
Mohammed HO, Starkey SR, Stipetic K, Divers TJ, Summers BA, de Lahunta A.Our previous studies implicated vitamin E deficiency as a risk factor for equine motor neuron disease, a possible model of human amyotrophic lateral sclerosis, and showed direct effects of this deficiency on brain vascular endothelium. To gain better understanding of the pathogenesis of equine motor neuron disease, we determined the effects of dietary antioxidant insufficiency and the resultant brain tissue oxidative stress on blood-brain barrier permeability. Rats (n = 40) were maintained on a diet deficient of vitamin E for 36 to 43 weeks; 40 controls were fed a normal diet. Permeability of ...
Geor R, Frank N.Obesity, insulin resistance, hyperinsulinemia and hypertriglyceridemia are components of an equine metabolic syndrome phenotype associated with increased laminitis risk in horses. Links between these conditions and laminitis must still be elucidated, but human medicine provides candidate mechanisms for future study, including inflammation associated with obesity, vascular compromise induced by insulin resistance, and endothelial dysfunction. Just as metabolic syndrome has been linked to cardiovascular disease in humans, studies are now required to determine the exact mechanisms responsible for...
Brooks AC, Menzies-Gow NJ, Wheeler-Jones C, Bailey SR, Cunningham FM, Elliott J.The endothelium plays a major role in the pathogenesis of endotoxemia. Binding of endotoxin (lipopolysaccharide; LPS) to endothelium initiates a range of signalling events, including activation of p38 mitogen activated protein kinases (MAPKs) that are involved in the initiation of inflammatory responses. In the present study we have examined whether clinically relevant concentrations of LPS can activate p38 MAPK in equine endothelial cells and have investigated the role of the kinase in neutrophil adhesion and mediator release. Cultured equine digital vein endothelial cells (EDVEC) were expose...
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 ...
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...
de la Rebière G, Franck T, Deby-Dupont G, Salciccia A, Grulke S, Péters F, Serteyn D.As heparins are sometimes used to prevent equine laminitis, the interactions between equine neutrophil myeloperoxidase (MPO), unfractionated (UFH) and fractionated low molecular weight (LMWH) heparins and digital endothelium have been investigated. The effects of the heparins on purified equine MPO activity were tested by immunocapture followed by enzymatic detection. Endothelium-MPO interactions were assessed by measuring total and active MPO uptake by arterial and venous digital endothelial cells in culture with or without the addition of heparins. A dose-dependent MPO inhibition by UFH and ...
Allen WR, Gower S, Wilsher S.Polyclonal antisera for vascular endothelial growth factor (VEGF) and its two main receptor molecules, VEGF-I (Flt) and VEGF-II (KDR), were used in a conventional immunocytochemical staining method to localize these angiogenic ligand molecules in the endometrium and placenta of the mare during the oestrous cycle and pregnancy. The anti-VEGF and anti-Flt sera both labelled the lumenal and glandular epithelia of the endometrium throughout the oestrous cycle and both the invasive trophoblast cells of the endometrial cups and the non-invasive trophoblast of the allantochorion in pregnancy. The ant...
Robertson TP, Moore JN, Noschka E, Lewis TH, Lewis SJ, Peroni JF.To determine the effects of inhibition of Rho-kinase or Src-family protein tyrosine kinases (srcPTK) on agonist-induced contractile responses in equine laminar arteries and veins. Methods: Laminar arteries and veins obtained from 13 adult mixed-breed horses. Methods: Laminar vessels were mounted on myographs and exposed to phenylephrine (PE), 5-hydroxytryptamine (5-HT), prostaglandin F(2) (PGF(2)), and endothelin-1 (ET-1) with or without the Rho-kinase inhibitor Y-27632 (10 microM), srcPTK inhibitor PP2 (10 microM), or a negative control analogue for PP2 (PP3; 10 microM). Results: Responses to...
Huang H, Lavoie-Lamoureux A, Moran K, Lavoie JP.Little is known concerning the possible contribution of T helper 2 (Th2)-type cytokines to the recruitment of neutrophils into the lung tissue. In the present study, endothelial cells from equine pulmonary arteries were cultured in the presence of recombinant equine (re) IL-4 and reIL-5, and the cytokine mRNA expression of molecules implicated in the chemotaxis and migration of neutrophils was studied using real-time RT-PCR. The functional response of reIL-4-induced endothelial cell stimulation on neutrophil migration was also studied using a chemotaxis chamber. ReIL-4 either increased the exp...
Padilla DJ, Epp TS, McDonough P, Marlin DJ, Erickson HH, Poole DC.During high intensity exercise, the very high pulmonary artery pressure (Ppa) experienced by Thoroughbred horses is considered a major factor in the aetiology of exercise-induced pulmonary haemorrhage (EIPH). Recently, endothelin-1 (ET-1), a potent vasoconstrictive hormone, has been found to increase Ppa in horses at rest via binding to its ET-1A receptor subtype. In addition, plasma concentrations of ET-1 are increased in horses during and after high intensity exercise. Objective: If ET-1 increases Ppa during exercise in the horse, administration of a specific ET-1A antagonist would decrease ...
Eades SC, Stokes AM, Johnson PJ, LeBlanc CJ, Ganjam VK, Buff PR, Moore RM.To quantify changes in endothelium-derived factors and relate those changes to various aspects of digital hemodynamics during the prodromal stages of carbohydrate overload (CHO)-induced laminitis in horses. Methods: 20 adult horses without abnormalities of the digit. Methods: Digital and jugular venous blood samples were collected at 1-hour intervals (for assessment of endothelin-1 [ET-1] immunoreactivity and measurement of glucose, insulin, and nitric oxide [NO] concentrations) or 4-hour intervals (CBC and platelet-neutrophil aggregate assessment) for 8 hours or 16 hours after induction of CH...
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...
Stokes AM, Venugopal CS, Hosgood G, Eades SC, Moore RM.The goals of this study were to determine the concentration-response (C-R) relationship of endothelin-1 (ET-1), compare 2 ET-receptor antagonists and determine the antagonist concentrations that block the vasomotor effects of ET-1, and compare the effectiveness of ET-1 and previously studied vasoconstrictors in equine palmar digital arterial and venous rings in vitro. Vessel rings from 8 nonlaminitic horses were placed in Tyrode's solution, 1 side fixed to the floor of an organ bath and the other side fixed to a force-displacement transducer. Two separate studies were conducted: (I) incubation...
Dubuc V, Lepault E, Theoret CL.Wound repair in horse limbs is often complicated by excessive fibroplasia and scarring. Occlusion of the microvessels populating the granulation tissue appears to be involved in the excessive accumulation of extracellular matrix during the repair of limb wounds. This study aimed to determine whether endothelial cell hypertrophy or hyperplasia, or both, contribute to microvascular occlusion and whether the pericyte is involved in this anomaly. We created 5 wounds, each 2.5 x 2.5 cm, on both forelimbs and on the body of 6 horses. One limb was bandaged to stimulate excessive wound fibroplasia. We...
Polikepahad S, Paulsen DB, Moore RM, Costa LR, Venugopal CS.To immunohistochemically determine the expression of endothelin (ET) receptors in bronchial smooth muscle and epithelium of healthy horses and horses affected by summer pasture-associated obstructive pulmonary disease (SPAOPD). Methods: Tissue specimens obtained from 8 healthy and 8 SPAOPD-affected horses. Methods: Horses were examined and assigned to healthy and SPAOPD groups. Horses were then euthanatized, and tissue specimens containing bronchi of approximately 4 to 8 mm in diameter were immediately collected from all lung lobes, fixed in zinc-formalin solution for 12 hours, and embedded in...
Hasebe R, Kimura T, Nakamura K, Ochiai K, Okazaki K, Wada R, Umemura T.Equine herpesvirus 1 (EHV-1) shows endotheliotropism in the central nervous system (CNS) of infected horses. However, infection of endothelial cells has not been observed in the CNS of infected mice. To explore the basis for this difference in endotheliotropism, we compared the susceptibility of equine brain microvascular endothelial cells (EBMECs) and mouse brain microvascular endothelial cells (MBMECs) to EHV-1 infection. The kinetics of viral growth in EBMECs was typical of a fully productive infection whereas viral infection in MBMECs seemed to be nonproductive. Immunofluorescence microsco...
Brindley MA, Maury W.Recently, it has become evident that entry of some retroviruses into host cells is dependent upon a vesicle-localized, low-pH step. The entry mechanism of equine infectious anemia virus (EIAV) has yet to be examined. Here, we demonstrate that wild-type strains of EIAV require a low-pH step for productive entry. Lysosomotropic agents that inhibit the acidification of internal vesicles inhibited productive entry of EIAV. The presence of ammonium chloride (30 mM), monensin (30 microM), or bafilomycin A (50 nM) in the medium dramatically decreased the number of EIAV antigen-positive cells. We foun...
Peroni JF, Moore JN, Noschka E, Grafton ME, Aceves-Avila M, Lewis SJ, Robertson TP.Equine laminitis is a crippling condition associated with a variety of systemic diseases. Although it is apparent that the prodromal stages of laminitis involve microvascular dysfunction, little is known regarding the physiology of this vasculature. The aim of the present study was to determine the relative responses of equine laminar arteries and veins to the vasoconstrictor agonists phenylephrine (1 nM-10 microM), 5-HT (1 nM-10 microM), PGF2alpha (1 nM-100 microM), and endothelin-1 (1 pM-1 microM). We have determined that laminar veins were more sensitive, with respect to the concentration o...
Chidambaram RM, Eades SC, Moore RM, Hosgood G, Venugopal CS.To characterize the in vitro response of equine cecal longitudinal smooth muscle (CLSM) to endothelin (ET)-1 and assess the role of ETA and ETB receptors in those ET-1-induced responses. Methods: 36 horses without gastrointestinal tract disease. Methods: To determine cumulative concentration-response relationships, CLSM strips were suspended in tissue baths containing graded concentrations of ET-1 (10(-9) to 10(-6)M) with or without BQ-123 (ETA receptor antagonist); with or without IRL-1038 (ETB receptor antagonist); or with both antagonists at concentrations of 10(-9), 10(-7), and 10(-5)M. To...
Mirza MH, Seahorn TL, Oliver JL, Hosgood G, Moore RM.The objective of the study was to determine whether nitric oxide (NO) is present in clinically healthy horses (control) under basal conditions, and if it increases secondary to naturally acquired strangulating large colon volvulus (affected). Eleven affected horses and 10 controls were studied. Jugular venous blood, abdominal fluid, and urine were collected. The NO concentrations were standardized to the creatinine concentration in the respective samples. A biopsy specimen collected from the large colon pelvic flexure at surgery was divided into subsections for processing for inducible nitric ...
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...
Wiemer P, Gruys E, van Hoeck B.The aim of this study was to investigate the biological behaviour of vascular grafts replacing a section of the jugular vein in order to improve the results of the surgical treatment of complete thrombosis of the jugular vein in the horse. Seven graft types: fresh allograft, home frozen allograft, glutaraldehyde-fixed allograft, cryo-preserved allograft, PTFE-graft (Gore), small intestinal submucosa preparation (Cook) and fresh autograft, were randomly implanted in ponies. The grafts were removed after one month and examined histologically for: preservation of the graft structures, acceptance ...
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...
Kumar P, Timoney JF.The stratified squamous epithelium of the lingual tonsil of five young horses was infiltrated with CD4 and CD8 positive cells, which were very numerous in the crypt reticular epithelium along with macrophages and IgGb and IgA positive cells. Lymphoid follicles of the lamina propria mucosae consisted of a parafollicular area, corona and germinal centre. The parafollicular area was populated by large numbers of CD4 and CD8 positive lymphocytes as well as macrophages, inter-digitating cells, and a few B-lymphocytes. The germinal centre contained mainly IgGb and IgG(T) positive cells, plasma cells...
Sayasith K, Bouchard N, Boerboom D, Brown KA, Doré M, Sirois J.Ovulation is accompanied by a marked infiltration of leukocytes into thecal layers after the gonadotropin surge. P-selectin is known to play a critical role in the initial steps of leukocyte recruitment from the bloodstream during inflammation. Thus, the objective was to investigate the potential regulation of P-selectin by gonadotropins in equine preovulatory follicles. The full-length equine P-selectin cDNA was cloned by a combination of reverse transcription-polymerase chain reaction (RT-PCR) and 5'- and 3'-rapid amplification of cDNA ends. Results showed that equine P-selectin cDNA encodes...
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...
Salter MM, Seeto WJ, DeWitt BB, Hashimi SA, Schwartz DD, Lipke EA, Wooldridge AA.To isolate and characterize endothelial colony-forming cells (ECFCs; a subtype of endothelial progenitor cells) from peripheral blood samples of horses. Methods: Jugular venous blood samples from 24 adult horses. Methods: Blood samples were cultured in endothelial cell growth medium. Isolated ECFCs were characterized by use of functional assays of fluorescence-labeled acetylated low-density lipoprotein (DiI-Ac-LDL) uptake and vascular tubule formation in vitro. Expression of endothelial (CD34, CD105, vascular endothelial growth factor receptor 2, and von Willebrand factor) and hematopoietic (C...
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...
Bailey SR, Wheeler-Jones C, Elliott J.5-hydroxytryptamine (5-HT; serotonin) is a potent vasoconstrictor of equine digital blood vessels and has been implicated in the pathogenesis of acute laminitis. Objective: The aims of this study were firstly to examine whether cells of the digital blood vessel wall exhibited an active uptake mechanism for 5-HT and to characterise its efficiency; and secondly, to study the potential inhibitory effect on this process of other amines, produced in the equine caecum. Methods: Confluent monolayers of equine digital vein endothelial cells (EDVEC) and equine digital vein smooth muscle cells (EDVSMC) ...
Baxter G.Endotoxin given in vivo has been shown to inhibit endothelial dependent relaxation, and augment adrenergic (norepinephrine) contractions in isolated palmar digital arteries of horses. A study, using tumor necrosis factor (TNF) in vitro, was performed to determine the possible cause of these vascular alterations. Palmar digital arteries were surgically removed from 6 horses under general anesthesia, cut into 4-mm vascular rings (4 segments/horse), suspended in tissue baths, and attached to force displacement transducers for measurement of vascular tension. Four in vitro treatment groups were ev...
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...
Lessiak U, Pratscher B, Tichy A, Nell B.Anti-VEGF agents were found to have clinical implications for the successful treatment of vascular-driven diseases in humans. In this study, a detailed biological characterization of bevacizumab in a variety of in vitro assays was carried out to determine the effect of bevacizumab on equine umbilical vein endothelial cells (EqUVEC). EqUVECs were harvested from umbilical cords of clinically healthy horses and exposed to different concentrations (1, 2, 4, 6, 8 mg/mL) of bevacizumab (Avastin). Assays concerning the drug's safety (cell viability and proliferation assay) and efficacy (cell tube for...
Blunden AS, Smith KC, Binns MM, Zhang L, Gower SM, Mumford JA.Equid herpesvirus 4 (EHV-4) infection was diagnosed as the cause of interstitial pneumonia in a 6-week-old conventionally reared Welsh pony foal, by cocultivation and immunolabelling with specific monoclonal antibodies, EHV-4 specific amplification of viral DNA, and immunohistological examination of infected tissues. The case was novel in that replication of the EHV-4 isolate in endothelial cells and in the synovial epithelium was a feature. Restriction digests of this isolate were compared with those of seven respiratory and one abortigenic EHV-4 isolate, and no differences in restriction pat...
Padilla DJ, Epp TS, McDonough P, Marlin DJ, Erickson HH, Poole DC.During high intensity exercise, the very high pulmonary artery pressure (Ppa) experienced by Thoroughbred horses is considered a major factor in the aetiology of exercise-induced pulmonary haemorrhage (EIPH). Recently, endothelin-1 (ET-1), a potent vasoconstrictive hormone, has been found to increase Ppa in horses at rest via binding to its ET-1A receptor subtype. In addition, plasma concentrations of ET-1 are increased in horses during and after high intensity exercise. Objective: If ET-1 increases Ppa during exercise in the horse, administration of a specific ET-1A antagonist would decrease ...
Wille KH, Schnorr B.Arterioles, precapillary sphincters, capillary endothelium, and pericytes probably regulate the blood flow in the intestinal microvascular bed similar to other regions of the body because of their equipment with contractile filaments. Only throttle veins with their arrangement of pools and their characteristics probably exert influence on the hemodynamic qualities of the blood flow in the intestinal mucosa.
Simonsen U, Prieto D, Hernández M, Sáenz de Tejada I, García-Sacristán A.The receptors mediating the contractions to both exogenously applied noradrenaline and electrical field stimulation (EFS) were characterized in horse isolated penile resistance arteries. The alpha 1-adrenoceptor-selective antagonist, prazosin, caused competitive rightward shifts of the contractile concentration-response curves (CRC) to phenylephrine. The alpha 2-antagonist, rauwolscine, also displaced to the right the CRC to the alpha 2-adrenoceptor-selective agonist, BHT 920. EFS (0.3 ms, 20-second trains) caused tetrodotoxin-sensitive frequency-dependent contractions which were enhanced in t...
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...
Dubuc V, Lepault E, Theoret CL.Wound repair in horse limbs is often complicated by excessive fibroplasia and scarring. Occlusion of the microvessels populating the granulation tissue appears to be involved in the excessive accumulation of extracellular matrix during the repair of limb wounds. This study aimed to determine whether endothelial cell hypertrophy or hyperplasia, or both, contribute to microvascular occlusion and whether the pericyte is involved in this anomaly. We created 5 wounds, each 2.5 x 2.5 cm, on both forelimbs and on the body of 6 horses. One limb was bandaged to stimulate excessive wound fibroplasia. We...
Wiemer P, Gruys E, van Hoeck B.The aim of this study was to investigate the biological behaviour of vascular grafts replacing a section of the jugular vein in order to improve the results of the surgical treatment of complete thrombosis of the jugular vein in the horse. Seven graft types: fresh allograft, home frozen allograft, glutaraldehyde-fixed allograft, cryo-preserved allograft, PTFE-graft (Gore), small intestinal submucosa preparation (Cook) and fresh autograft, were randomly implanted in ponies. The grafts were removed after one month and examined histologically for: preservation of the graft structures, acceptance ...
McKeever KH, Antas LA, Kearns CF.The objective of the present study was to measure plasma endothelin-1 (ET-1) at rest and during exercise in the horse. Six healthy, Standardbred and Thoroughbred mares (5.3+/-0.8 years; 445.2+/-13.1 kg) which were unfit, but otherwise accustomed to running on the treadmill, were used in the study. Plasma ET-1 concentrations were measured using a commercially available radioimmunoassay kit. Horses performed three trials: a standing control (CON) trial where blood was collected from the jugular vein every minute for 5 min; a graded exercise test (GXT) where blood samples were collected at the en...
Ledbetter EC, Irby NL.To describe the corneal in vivo confocal microscopy (IVCM) findings in horses with putative immune-mediated keratitis (IMMK). Methods: Sixty five horses with IMMK. Methods: Horses diagnosed with IMMK were examined with a modified Heidelberg Retina Tomograph II and Rostock Cornea Module. The findings from the IVCM examinations were correlated with clinical details from ophthalmic examination and diagnostic test results. Results: Eighty eyes from 65 horses were examined. Clinical IMMK lesions were categorized as epithelial (n = 17 eyes), superficial stromal (n = 38), midstromal (n = 18), a...
Benamou AE, Marlin DJ, Callingham BC, Hiley RC, Lekeux R.There is currently little published information about the effects of endothelin-1 (ET-1), a potent endogenous spasmogen of vascular and airway smooth muscle, on pulmonary vasculature and airways or which ET receptor subtypes mediate ET-1-induced vasoconstrictive and bronchoconstrictive action in the horse. Objective: To investigate the effect of endothelin-1 (ET-1) on smooth muscle from isolated equine pulmonary artery and bronchus. In addition, the roles of ETA and ETB receptors in ET-1 mediated contraction in these tissues were assessed. Methods: The force generation of ring segments from pu...
Polikepahad S, Paulsen DB, Moore RM, Costa LR, Venugopal CS.To immunohistochemically determine the expression of endothelin (ET) receptors in bronchial smooth muscle and epithelium of healthy horses and horses affected by summer pasture-associated obstructive pulmonary disease (SPAOPD). Methods: Tissue specimens obtained from 8 healthy and 8 SPAOPD-affected horses. Methods: Horses were examined and assigned to healthy and SPAOPD groups. Horses were then euthanatized, and tissue specimens containing bronchi of approximately 4 to 8 mm in diameter were immediately collected from all lung lobes, fixed in zinc-formalin solution for 12 hours, and embedded in...
Söder J, Bröjer JT, Nostell KE.Systemic hypertension is a prominent feature in humans with metabolic syndrome (MS) and this is partly caused by an enhanced endothelin-1 (ET-1) mediated vasoconstriction. There are indications that systemic hypertension might be a feature in equine metabolic syndrome (EMS) but if ET-1 is involved in the development of hypertension in horses is not known. Increased levels of cortisol have also been found in humans with MS but there are no reports of this in horses. Before blood pressure, plasma ET-1 and serum cortisol can be evaluated in horses with EMS, it is necessary to investigate the inte...
Wunn D, Wardrop KJ, Meyers K, Kramer J, Ragle C.To develop methods to isolate, culture, and characterize equine hoof endothelial cells (EC) and keratinocytes. Methods: Cells harvested from the forelimbs of 8 horses. Methods: EC were obtained via catheters placed in the palmar digital arteries of the disarticulated lower portion of the forelimbs from 4 horses that had been heparinized prior to euthanasia. Phosphate-buffered saline solution was used to remove and discard RBC from blood vessels, and collagenase was used to loosen and flush EC from the vasculature. Hoof keratinocytes were obtained from 4 recently euthanatized horses by use of d...
Sharpe AN, Seeto WJ, Winter RL, Zhong Q, Lipke EA, Wooldridge AA.OBJECTIVE To evaluate optimal isolation of endothelial colony-forming cells (ECFCs) from peripheral blood of horses. SAMPLE Jugular and cephalic venous blood samples from 17 adult horses. PROCEDURES Each blood sample was divided; isolation was performed with whole blood adherence (WBA) and density gradient centrifugation (DGC). Isolated cells were characterized by uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-labeled acetylated low-density lipoprotein (DiI-Ac-LDL), vascular tubule formation, and expression of endothelial (CD34, CD105, vascular endothelial growth ...
Robertson TP, Moore JN, Noschka E, Lewis TH, Lewis SJ, Peroni JF.To determine the effects of inhibition of Rho-kinase or Src-family protein tyrosine kinases (srcPTK) on agonist-induced contractile responses in equine laminar arteries and veins. Methods: Laminar arteries and veins obtained from 13 adult mixed-breed horses. Methods: Laminar vessels were mounted on myographs and exposed to phenylephrine (PE), 5-hydroxytryptamine (5-HT), prostaglandin F(2) (PGF(2)), and endothelin-1 (ET-1) with or without the Rho-kinase inhibitor Y-27632 (10 microM), srcPTK inhibitor PP2 (10 microM), or a negative control analogue for PP2 (PP3; 10 microM). Results: Responses to...
Rieger J, Hopperdietzel C, Kaessmeyer S, Slosarek I, Diecke S, Richardson K, Plendl J.Human and equine patients are known to frequently develop vascular complications, particularly thrombosis both in veins and arteries as well as in the microvasculature. Objective: The aim of the present study was to investigate and compare the angiogenic response of human and equine endothelial cells to lesions in an in vitro scratch assay. Methods: Endothelial cells from human umbilical vein (HUVEC), abdominal aorta (HAAEC) and dermal microvasculature (HDMEC) as well as equine carotid artery (EACEC) and jugular vein (EVJEC) were cultured and an elongated defect was created (scratch or "wound"...
Katz LM, Marr CM, Elliott J.To compare the responses of equine digital arteries (EDAs) and equine digital veins (EDVs) to endothelin-1 (ET-1) and determine the role of the endothelium and type of receptors involved in the modulation and mediation of those responses, respectively. Methods: 5 to 9 palmar digital vessels/experiment from 28 healthy horses. Methods: Rings of dissected vessels were mounted under tension between force transducer wires in organ baths containing Krebs-Henseleit solution at 30 degrees C. Responses of EDAs and EDVs (with intact [+e] or denuded [-e] endothelium) to cumulative concentrations of ET-1 ...
Cogswell AM, Johnson PJ, Adams HR.To test the hypothesis that endothelium-derived nitric oxide modulates vasomotor reactivity in equine digital arteries. Methods: Digital arteries were isolated from adult horses, and their vasodilator properties were examined in an in vitro controlled environment. Methods: Five adult horses (1 gelding, 4 mares) without evidence of hoof or vascular disease were studied. Methods: Arterial rings with or without endothelium were exposed to endothelium-dependent vasodilator drugs in the presence or absence of a pharmacologic inhibitor of the enzyme nitric oxide synthase. Results: Vasodilator effect...
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...
Eades SC, Stokes AM, Johnson PJ, LeBlanc CJ, Ganjam VK, Buff PR, Moore RM.To quantify changes in endothelium-derived factors and relate those changes to various aspects of digital hemodynamics during the prodromal stages of carbohydrate overload (CHO)-induced laminitis in horses. Methods: 20 adult horses without abnormalities of the digit. Methods: Digital and jugular venous blood samples were collected at 1-hour intervals (for assessment of endothelin-1 [ET-1] immunoreactivity and measurement of glucose, insulin, and nitric oxide [NO] concentrations) or 4-hour intervals (CBC and platelet-neutrophil aggregate assessment) for 8 hours or 16 hours after induction of CH...
Windberger U, Auer R, Seltenhammer M, Mach G, Skidmore JA.From a certain level of exercise-intensity onward, hematocrit increases in horses, which brings more oxygen carriers into the bloodstream. Camels, however, when used in competitive racing could be even in need of iron supplementation and blood transfusions due to a severe reduction of their available hematocrit compared to their resting hematocrit. Since the extrinsic and intrinsic mechanical properties of camel erythrocytes (RBC) are so different compared to RBCs of other mammals, the question arises whether this observation might be a response to endurance exercise aiming at keeping the RBC ...
Goehring LS, Brandes K, Ashton LV, Wittenburg LA, Olea-Popelka FJ, Lunn DP, Soboll Hussey G.Equine herpesvirus-associated myeloencephalopathy is the result of endothelial cell infection of the spinal cord vasculature with equine herpesvirus-1 (EHV-1) during cell-associated viraemia. Endothelial cell infection requires contact between infected peripheral blood mononuclear and endothelial cells. Inflammation generated during viraemia likely upregulates adhesion molecule expression on both cell types increasing contact and facilitating endothelial cell infection. Objective: Evaluating the role of anti-inflammatory drugs in decreasing endothelial cell infection with EHV-1. Methods: In vi...
Gorelkin L, Jahrling PB.Pancreatic tissue from hamsters inoculated with a virulent strain of Venezuelan equine encephalomyelitis virus (VEE) was studied sequentially with fluorescent antibody, light and electron microscopic technics. Progressive viral growth and cellular necrosis in the pancreas were demonstrated. Pancreatic infection resulted from both viremia and direct extension from the spleen across contaminated serosal planes. Mature viruses traversed the endothelium within endothelial vesicles and were associated with acinar as well as islet cells.
