Evaluation of beta3-adrenoceptor-mediated relaxation in intact and endotoxin-treated equine digital veins.

OBJECTIVE 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. SAMPLE POPULATION Forelimbs obtained from 30 horses. PROCEDURE 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, ZD 2079, and ZM 215001 induced concentration-dependent relaxation. Isoprenaline and SR 58611A-induced relaxations were reduced or unaffected by nadolol, respectively. In intact EDVs, SR 58611A-induced relaxation was significantly reduced in the presence of 2 microM ZM 215001 (used as a beta3-AR antagonist). In endothelium-denuded EDVs or intact EDVs in the presence of a nitric oxide synthase inhibitor, isoprenaline and SR 58611A-induced relaxations were significantly decreased. The endothelium-independent relaxation to SR 58611A was significantly inhibited in the presence of ZM 215001. In endotoxin-treated EDV, isoprenaline- and SR 58611A-induced relaxations were significantly reduced. In these conditions, cycloheximide (a protein synthesis inhibitor) and ibuprofen (a cyclooxygenase inhibitor) restored the relaxant response to SR 58611A. CONCLUSIONS AND CLINICAL RELEVANCE Beta3-adrenoceptors are functionally expressed in EDVs. Incubation in the presence of endotoxin, used as an in vitro model of laminitis, induced an alteration of beta-AR-mediated relaxations in EDVs, which could be the consequence of cyclooxygenase induction and subsequent prostanoid production.

[1]  M. Gogny,et al.  Effect of moderate cooling on contractile responses in mouse vas deferens and its relation to calcium , 1995, Naunyn-Schmiedeberg's Archives of Pharmacology.

[2]  J. Balligand,et al.  β_3-Adrenoceptors in the cardiovascular system , 2000 .

[3]  A. Shaw,et al.  Role of endothelium/nitric oxide in atypical beta-adrenoceptor-mediated relaxation in rat isolated aorta. , 2000, European journal of pharmacology.

[4]  A. Nolan,et al.  The role of nitric oxide in the responses of the ovine digital artery to vasoactive agents and modification of these responses by endotoxin and cytokines , 2000, British journal of pharmacology.

[5]  J. Mironneau,et al.  Beta‐3 adrenergic stimulation of L‐Type Ca2+ channels in rat portal vein myocytes , 2000, British journal of pharmacology.

[6]  P. Devillier,et al.  Thromboxane A2 modulates cyclic AMP relaxation and production in human internal mammary artery , 2000 .

[7]  C. Gauthier,et al.  Beta 3‐adrenoceptor stimulation induces vasorelaxation mediated essentially by endothelium‐derived nitric oxide in rat thoracic aorta , 1999, British journal of pharmacology.

[8]  D. Hood The pathophysiology of developmental and acute laminitis. , 1999, The Veterinary clinics of North America. Equine practice.

[9]  S. Bailey,et al.  The role of prostanoids and nitric oxide in endotoxin-induced hyporesponsiveness of equine digital blood vessels. , 1999, Equine veterinary journal.

[10]  S. Eades,et al.  Palmar digital vessel relaxation in healthy horses and in horses given carbohydrate. , 1999, American journal of veterinary research.

[11]  E. Tagaya,et al.  Atypical adrenoceptor-mediated relaxation of canine pulmonary artery through a cAMP-dependent pathway. , 1998, Biochemical and biophysical research communications.

[12]  G. Baxter,et al.  Evaluation of digital and laminar blood flow in horses given a low dose of endotoxin. , 1998, American journal of veterinary research.

[13]  F. Arioli,et al.  Differences between longitudinal and circular smooth muscle in beta-adrenergic control of motility of isolated equine ileum. , 1997, American journal of veterinary research.

[14]  C. Kamei,et al.  Effect of Apafant on bronchial hyperresponsiveness and down-regulation of beta-adrenoceptors induced by endotoxin in guinea pigs. , 1997, Arzneimittel-Forschung.

[15]  A. Vu,et al.  Loss of nitric oxide release in passively sensitized guinea‐pig aorta with purified immunoglobulin Gl , 1997, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[16]  A. J. Thompson,et al.  The acid metabolite of ZD7114 is a partial agonist of lipolysis mediated by the rat beta 3-adrenoceptor. , 1996, European journal of pharmacology.

[17]  I. Henderson,et al.  Nitric oxide donors as treatment for grass induced acute laminitis in ponies. , 1996, Equine veterinary journal.

[18]  G. Baxter Alterations of endothelium-dependent digital vascular responses in horses given low-dose endotoxin. , 1995, Veterinary surgery : VS.

[19]  C. Lugnier,et al.  Isoprenaline induces endothelium-independent relaxation and accumulation of cyclic nucleotides in the rat aorta. , 1994, European journal of pharmacology.

[20]  M. Nakazawa,et al.  [Research and development of ozagrel, a highly selective inhibitor of TXA2 synthase]. , 1994, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan.

[21]  H. Adams,et al.  INHIBITION OF ENDOTHELIUM‐DEPENDENT VASODILATION BY ESCHERICHIA COLI ENDOTOXEMIA , 1994, Shock.

[22]  M. Oriowo Atypical β‐adrenoceptors in the rat isolated common carotid artery , 1994 .

[23]  C. Bryant,et al.  The role of nitric oxide in the responses of equine digital veins to vasodilator and vasoconstrictor agents. , 1994, Equine veterinary journal.

[24]  J. Mckillop,et al.  The role of cytokines in the production of prostacyclin and thromboxane in human mononuclear cells. , 1994, Immunological investigations.

[25]  G. Baxter,et al.  Effects of tumor necrosis factor on in vitro digital arterial responses in horses. , 1994, American journal of veterinary research.

[26]  S. Vatner,et al.  Peripheral vascular effects of beta-3 adrenergic receptor stimulation in conscious dogs. , 1994, The Journal of pharmacology and experimental therapeutics.

[27]  J. Moore,et al.  Correlation of clinical and laboratory data with serum tumor necrosis factor activity in horses with experimentally induced endotoxemia. , 1990, American journal of veterinary research.

[28]  J. Moore,et al.  Evaluation of equine digital Starling forces and hemodynamics during early laminitis. , 1990, American journal of veterinary research.

[29]  J. Moore,et al.  Effect of endotoxin administration on equine digital hemodynamics and starling forces. , 1990, American journal of veterinary research.

[30]  J. Moore,et al.  In vitro reactivity of digital arteries and veins to vasoconstrictive mediators in healthy horses and in horses with early laminitis. , 1989, American journal of veterinary research.

[31]  Terrence P. Kenakin,et al.  A Pharmacologic Analysis of Drug-Receptor Interaction , 1987 .

[32]  H. Garner,et al.  Plasma endotoxin levels in horses subjected to carbohydrate induced laminitis. , 1987, Equine veterinary journal.

[33]  G. Hardee,et al.  Modulation of arachidonic acid metabolism in endotoxic horses: comparison of flunixin meglumine, phenylbutazone, and a selective thromboxane synthetase inhibitor. , 1986, American journal of veterinary research.