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Abstract

Desensitization of the beta-2 adrenoceptor-mediated vasodilation in rat aorta after prolonged treatment with the beta-2 adrenoceptor agonist clenbuterol.

M G Kazanietz and M A Enero
Journal of Pharmacology and Experimental Therapeutics February 1990, 252 (2) 758-764;
M G Kazanietz
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M A Enero
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Abstract

Administration to rats of the selective beta-2 adrenoceptor agonist (+/-)-clenbuterol (CLEN) (0.3 mg.kg-1 s.c., twice daily for 14 days) decreased the relaxant responses to the beta adrenoceptor agonist (-)-isoproterenol (IS) and to CLEN in KCl-contracted aortic rings. The treatment did not modify the vasodilation induced by forskolin (a direct activator of the catalytic subunit of the adenylate cyclase), 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor), adenosine or acetylcholine. IS increased (cAMP) cyclic AMP levels dose-dependently in rat aorta, and this effect was reduced markedly in arteries from CLEN-treated rats. By contrast, the treatment did not modify the forskolin-induced cAMP production. The contractile response to (-)-norepinephrine (NE) was inhibited in the presence of IS or CLEN in control aortic rings. However, this modulatory effect was not seen in arteries from CLEN-treated rats. Preincubation of the arteries with either cholera toxin (an activator of the stimulatory guanine nucleotide binding protein, Gs) or forskolin reduced NE-induced vasoconstriction to the same extent in aortic rings from both control and CLEN-treated rats. The chronotropic response to NE in rat atria (beta-1-mediated) was not affected by the treatment. These results suggest that prolonged administration of CLEN to rats induced desensitization of beta-2 adrenoceptor-mediated vascular relaxation by alterations at the level of the beta-2 adrenergic receptor, but not in the mechanisms related to Gs, adenylate cyclase or in those distal to cAMP production.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 252, Issue 2
1 Feb 1990
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Abstract

Desensitization of the beta-2 adrenoceptor-mediated vasodilation in rat aorta after prolonged treatment with the beta-2 adrenoceptor agonist clenbuterol.

M G Kazanietz and M A Enero
Journal of Pharmacology and Experimental Therapeutics February 1, 1990, 252 (2) 758-764;

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Abstract

Desensitization of the beta-2 adrenoceptor-mediated vasodilation in rat aorta after prolonged treatment with the beta-2 adrenoceptor agonist clenbuterol.

M G Kazanietz and M A Enero
Journal of Pharmacology and Experimental Therapeutics February 1, 1990, 252 (2) 758-764;
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