Adrenergic regulation of vascular smooth muscle tone in calf digital artery.
Radioligand binding studies and functional assays on isolated smooth muscle preparations were performed in order to obtain a biochemical and functional characterization of the beta-adrenoceptor (beta-AR) subtypes involved in regulation of the smooth muscle relaxation of the calf's common digital artery. The results indicate that the common digital artery possesses two beta-AR populations (40% beta(1) and 60% beta(2)) and the beta(2)-subtype appears to predominate as far as function is concerned. Only the beta(2)-AR agonists clenbuterol and fenoterol caused dose-related relaxant effects, antagonized by propranolol, when tested in preparations precontracted both with PGF(2alpha) (1.4 x 10(-5) m) and noradrenaline (1.2 x 10(-6) m). In noradrenaline precontracted preparations the beta(1)-AR selective agonists dobutamine and xamoterol caused vasodilation which was not antagonized by (+/-)propranolol. While the functional relaxant effects of dobutamine may be attributed to its potent competitive alpha-AR blocking activity, further investigations are required to explain the effect of xamoterol. The vasodilator effect of (+/-)isoproterenol was irregular. The recorded contractile effects, mainly at dosages greater than 10(-6) m, suggest the loss of drug selectivity for beta-AR and alpha-AR activation. Indirect evidence indicates that the alpha-adrenoceptor (alpha-AR) population in this tissue which produces a strong contraction is functionally dominant over the beta-AR, suggesting limited therapeutic benefit for beta-AR drugs to control blood flow disorders in the calf's distal limb.
Department of Animal Health and Welfare, Division of Veterinary Pharmacology and Toxicology, University of Bari, Valenzano, Italy.
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C
Belloli
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Badino
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F
Arioli
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Odore
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D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001158:Arteries / Q000187:drug effects*; D002417:Cattle; D002418:Cattle Diseases / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005552:Forelimb / Q000098:blood supply; D007794:Lameness, Animal / Q000503:physiopathology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta