Vascular alpha-1 antagonistic and agonistic effects of beta adrenoceptor agonists in rabbit common carotid arteries.
The stainless-steel cannula-inserting method was used to observe vascular effects of mixed and selective beta adrenoceptor agonists, isoproterenol, procaterol and denopamine, on isolated, perfused rabbit common carotid arteries. In phenylephrine-preconstricted preparations, the three beta agonists induced a dose-dependent vasodilation which was not suppressed by treatment with beta antagonists, atenolol, a selective beta-1 antagonist and ICI 118551, a selective beta-2 antagonist. On the other hand, in prostaglandin F2 alpha-preconstricted preparations, these agonists produced no vasodilation and revealed weak vasoconstrictions which were readily suppressed by bunazosin, a selective alpha-1 antagonist. Moreover, these agonists caused a shift of the dose-response curve for phenylephrine to the right in a parallel fashion in non-preconstricted preparations. The relative pA2 values for isoproterenol, procaterol and denopamine calculated from the displacement curve were 7.47, 7.59 and 8.17, respectively. Thus, it is concluded that 1) there are little functional beta adrenoceptors in the rabbit common carotid arteries, 2) beta adrenoceptor agonists have both antagonistic and agonistic properties for alpha-1 adrenoceptor activation, 3) denopamine possesses a higher potency as an alpha-1 antagonist and 4) beta agonists generally act as vasodilators in rabbit cerebral circulation.
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
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Fujiwara
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Chiba
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000378:metabolism; D015237:Dinoprost; D004983:Ethanolamines / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010477:Perfusion; D010656:Phenylephrine; D017265:Procaterol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; C026777:ICI 118551; D001262:Atenolol; D015237:Dinoprost; D007545:Isoproterenol; C037293:denopamine; D017265:Procaterol