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- Author or Editor: Rustin M. Moore x
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Abstract
Objective—To characterize the in vitro response of circular and longitudinal myometrial layers of the uterine horn (CMLH and LMLH, respectively) of horses to endothelin (ET)-1 by use of specific ETA (BQ-123) and ETB (IRL-1038) receptor antagonists.
Sample Population—Uteruses from 10 nongravid mares in anestrus.
Procedure—Muscle strips from the CMLH and LMLH were suspended in tissue baths and connected to force-displacement transducers interfaced with a polygraph. Strips were incubated for 45-minute intervals with no antagonist (control specimens), and 3 concentrations (10–9, 10–7, and 10–5M) of BQ-123, IRL- 1038, or BQ-123 and IRL-1038 before concentrationresponse curves to ET-1 were generated. Contractile response to cumulative concentrations of ET-1 (10–9 to 10–6M) was quantified by measuring change in the area under the curve (AUC) for the 3-minute period after each ET-1 dose.
Results—ET-1 caused concentration-dependent contraction of the CMLH and LMLH specimens. Application of BQ-123 decreased AUC values for both layers. Application of IRL-1038 increased the AUC value for LMLH specimens but did not affect the CMLH value. The combination of BQ-123 and IRL-1038 decreased the AUC value for LMLH tissue and increased that for CMLH tissue.
Conclusions and Clinical Relevance—ET-1 causes contraction of the CMLH and LMLH in nongravid horses. In both layers, ETA receptors mediate contraction but the role of ETB receptors remains unclear. In the LMLH, ETA receptors have a dominant role; the presence of another receptor or receptor subtype within this layer is suggested. These findings support a physiologic role for ET-1 in uterine contractility. (Am J Vet Res 2005;66:1094–1100)
Abstract
Objective—To establish an in vivo method for matrix metalloproteinase (MMP)-2 and MMP-9 induction in horses via IV administration of lipopolysaccharide (LPS) and to evaluate the ability of doxycycline, oxytetracycline, flunixin meglumine, and pentoxifylline to inhibit equine MMP-2 and MMP-9 production.
Animals—29 adult horses of various ages and breeds and either sex.
Procedures—In part 1, horses received an IV administration of LPS (n = 5) or saline (0.9% NaCl) solution (5). Venous blood samples were collected before and at specified times for 24 hours after infusion. Plasma was harvested and analyzed for MMP-2 and MMP-9 activities via zymography. In part 2, horses received doxycycline (n = 5), oxytetracycline (5), flunixin meglumine (5), or pentoxifylline (4) before and for up to 12 hours after administration of LPS. Plasma was obtained and analyzed, and results were compared with results from the LPS-infused horses of part 1.
Results—Administration of LPS significantly increased MMP-2 and MMP-9 activities in the venous circulation of horses. All MMP inhibitors significantly decreased LPS-induced increases in MMP activities but to differing degrees. Pentoxifylline and oxytetracycline appeared to be the most effective MMP-2 and MMP-9 inhibitors, whereas doxycycline and flunixin meglumine were more effective at inhibiting MMP-2 activity than MMP-9 activity.
Conclusions and Clinical Relevance—IV administration of LPS to horses caused increased venous plasma activities of MMP-2 and MMP-9. These MMP activities were reduced by pentoxifylline and oxytetracycline, suggesting that further evaluation of these medications for treatment and prevention of MMP-associated diseases in horses is indicated.
Abstract
Objective—To evaluate the in vitro effects of adenosine tryphosphate (ATP) on vasomotor tone of equine colonic vasculature.
Sample Population—Arteries and veins from the left ventral colon of 14 mixed-breed horses euthanatized for reasons unrelated to cardiovascular or gastrointestinal tract disease.
Procedures—Endothelium-intact and -denuded arterial and venous rings were precontracted with 10–7 and 1.8 × 10–8 M endothelin-1, respectively. In 1 trial, endothelium-intact rings were also incubated with 10–4 M Nω-nitro-L-arginine methyl ester (L-NAME) to inhibit nitric oxide (NO) production. Adenosine triphosphate (10–8 to 10–3 M) was added in a noncumulative manner, and relaxation percentage versus time curves were generated. Areas under the curves (ie, percentage of relaxation time) were calculated.
Results—Relaxation response of arterial and venous rings to ATP was dose-dependent. Percentage of relaxation time in response to 10–4 and 10–3 M ATP was significantly greater, compared with that for rings not treated with ATP. Removal of endothelium attenuated but did not eliminate the relaxation response. Addition of L-NAME did not attenuate the relaxation response in arteries. At higher concentrations, the vascular response to ATP was biphasic.
Conclusions and Clinical Relevance—ATP applied to equine colonic arterial and venous rings with and without intact endothelium induced a biphasic response characterized by transient contraction followed by slow, substantial, and sustained relaxation. This ATP-induced response is possibly mediated by a mechanism other than NO. Adenosine triphosphate may be a useful treatment to modulate colonic vasomotor tone in horses with strangulating volvulus of the ascending colon. (Am J Vet Res 2001;62:1928–1933)
Abstract
Objective—To evaluate the effectiveness of 2 potential endothelin (ET)-1 antagonists in blocking the contractile responses of equine colonic vessels to increasing concentrations of ET-1.
Sample Population—Mesenteric vessels from 6 clinically healthy horses.
Procedure—Colonic vessels (arterial and venous rings) were placed in organ baths with oxygenated Tyrode solution at 37 C. Each was attached to a force transducer interfaced with a polygraph, and 2 g of tension was applied and equilibrated for 45 minutes. Then, B-1 (PD 142893) and B-2 (PD 145065) ET-1 antagonists were tested. One ring from each vessel type was used as a control for determining concentration- response relationships of ET-1 (10–10 to 10–6 M). Three rings of each vessel type were incubated with 3 concentrations of each antagonist (10–7, 10–6, and 10 –5 M) for 30 minutes before ET induced contractions were determined. The maximum contractile response and pA2 values were determined.
Results—Vessels contracted in a concentrationdependent manner to ET-1. Arteries responded slowly but reached greater contractions. Veins responded immediately with sustained contractions. Both antagonists inhibited contractions in a concentrationdependent manner with significant differences at 10–6 and 10–5 M for arteries and 10–5 M for veins. Complete blockade of contractions was observed with B-2 (10–5 M). The pA2 values for B-1 were 8.26 and 6.82 for arteries and veins, respectively, whereas they were 8.25 and 7.21 for B-2.
Conclusion and Clinical Relevance—Both antagonists effectively blocked ET-1-induced contractions of equine colonic vessels. Because B-2 is water soluble and caused complete blockade at 10–5 M, it appears to be the preferred antagonist. (Am J Vet Res 2001;62:154–159)
Abstract
Objective—To compare responses of bronchial rings obtained from healthy horses and horses affected with summer pasture-associated obstructive pulmonary disease (SPAOPD) to selected mediators of airway hyperreactivity in vitro.
Sample Population—Bronchial rings from 6 healthy horses and 6 horses affected with SPAOPD.
Procedure—Bronchial rings obtained from each group of horses were mounted in organ baths and attached to force transducers interfaced with a polygraph. After applying 2g of tension, each ring was allowed to equilibrate for 45 minutes in Tyrode's solution at 37 C. Cumulative concentration-response relationships to graded concentrations of selected mediators (10–8 to 10–4 M ) were determined and analyzed for significance at each concentration.
Results—Acetylcholine, histamine, 5-hydroxytryptamine, and leukotriene D4 induced concentrationdependent contractile responses in bronchial rings. Prostaglandin F2α induced weak and inconsistent contractile responses. The other 2 agents, norepinephrine and substance P, did not induce concentrationdependent responses. Considering the overall groupdrug effect, acetylcholine, histamine, 5-hydroxytryptamine, and leukotriene D4 were effective in inducing consistent concentration-dependent contractile responses in both groups. Only 5-hydroxytryptamine and histamine induced significant responses in contractility between groups. The response of bronchial rings from horses with SPAOPD to 5-hydroxytryptamine was significantly greater than those from control horses, whereas the response to histamine was significantly lower. Significant responses were evident at concentrations ranging from 10–6 to 10–4 M for both drugs.
Conclusions and Clinical Relevance—Because the airways of horses with SPAOPD had increased responsiveness to 5-hydroxytryptamine in vitro, treatment modalities using 5-hydroxytryptamine antagonists should be investigated to address this phenomenon. (Am J Vet Res 2001;62:259–263).
Abstract
Objective—To correlate clinical score, intrapleural pressure, cytologic findings of bronchoalveolar lavage fluid (BALF), and histologic lesions of pulmonary tissue in horses affected with summer pasture-associated obstructive pulmonary disease (SPAOPD).
Animals—8 adult horses affected with SPAOPD and 6 adult horses without evidence of respiratory tract disease.
Procedure—Clinical score, change in intrapleural pressure (ΔPpl) during tidal breathing, results of cytologic examination and bacteriologic culture of BALF, and results of histologic examination of pulmonary parenchyma were evaluated.
Results—Clinical scores for SPAOPD-affected horses (median, 5.75; range, 4.0 to 7.5) were significantly greater, compared with clinically normal horses (median, 2.0; range, 2.0 to 3.0). Cytologic examination of BALF from SPAOPD-affected horses revealed predominantly nondegenerate neutrophils. Histologic lesions were identified throughout pulmonary tissue and included severe accumulation of mucus and neutrophils within the small airways, metaplasia of bronchiolar goblet cells, and mild peribronchial infiltrate. Histologic examination of specimens collected via percutaneous biopsy was predictive of disease and corresponded to findings at postmortem examination. Clinical score and δPpl were highly correlated with mucus accumulation in the airways of affected horses. Peribronchial inflammatory infiltrate correlated with percentage of neutrophils in BALF of affected horses.
Conclusions and Clinical Relevance—Clinical scoring and ΔPpl provided valid estimates of disease severity. Findings from cytologic examination of BALF of SPAOPD-affected horses varied, although, in most instances, it was diagnostically useful. Severe mucus accumulation in the airways was the most remarkable histopathologic finding in SPAOPDaffected horses. Examination of biopsy specimens collected from pulmonary parenchyma was consistently useful in diagnosing SPAOPD. (Am J Vet Res 2000;61:167–173)
Abstract
Objective—To characterize alterations in systemic and local colonic hemodynamic variables associated with IV infusion of ATP-MgCl2 in healthy anesthetized horses.
Animals—12 adult horses.
Procedure—Six horses were given ATP-MgCl2, IV, beginning at a rate of 0.1 mg of ATP/kg of body weight/min with incremental increases until a rate of 1.0 mg/kg/min was achieved. The remaining 6 horses were given an equivalent volume of saline (0.9% NaCl) solution over the same time period. Colonic and systemic hemodynamic variables and colonic plasma nitric oxide (NO) concentrations were determined before, during, and after infusion.
Results—Infusion of ATP-MgCl2 caused a rate-dependent decrease in systemic and colonic vascular resistance, principally via its vasodilatory effects. A rate of 0.3 mg of ATP/kg/min caused a significant decrease in systemic and colonic arterial pressure and colonic vascular resistance without a significant corresponding decrease in colonic arterial blood flow. Consistent alterations in NO concentrations of plasma obtained from colonic vasculature were not detected, despite profound vasodilatation of the colonic arterial vasculature.
Conclusions and Clinical Relevance—Results revealed that IV infusion of ATP-MgCl2 may be beneficial in maintaining colonic perfusion in horses with ischemia of the gastrointestinal tract, provided a sufficient pressure gradient exists to maintain blood flow. (Am J Vet Res 2001;62:1240–1249)
Abstract
Objective—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).
Animals—7 adult horses with SPAOPD and 6 clinically normal adult horses.
Procedure—Severity of SPAOPD was determined by use of clinical scores, change in intrapleural pressure (ΔPpl) 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 fluid (ELF) were determined by use of a chemiluminescent method. Inducible nitric oxide synthase (iNOS) and nitrotyrosine (NT) were localized in formalin-fixed lung specimens by use of immunohistochemical staining, and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) activity was localized in cryopreserved specimens by use of histochemical staining.
Results—Plasma concentration of NO in affected horses was slightly but not significantly greater than concentration in nonaffected horses. Nitric oxide concentrations in BALF or ELF did not differ between groups. Immunoreactivity of iNOS in bronchial epithelial cells of 3 of 5 lung lobes was greater in horses with SPAOPD, compared with nonaffected horses. However, staining for NT and NADPHd activity did not differ between groups.
Conclusions and Clinical Relevance—Expression of iNOS was greater in bronchial epithelial cells of horses with SPAOPD, compared with nonaffected horses, suggesting that NO may play a role in amplifying the inflammatory process in the airways of horses with this disease. (Am J Vet Res 2001;62:1381–1386)
Abstract
“You cannot change any society unless you take responsibility for it, unless you see yourself belonging to it, and responsible for changing it.”
– Grace Lee Boggs
