Vascular responses to beta-adrenoceptor subtype-selective agonists with and without endothelium in rat common carotid arteries.
1. Using the cannula inserting method, vasodilator responses to beta-adrenoceptor agonists (isoprenaline, denopamine and procaterol) were investigated in isolated and perfused rat common carotid arteries. 2. Each beta-adrenoceptor agonist induced a vasodilation in preparations preconstricted by phenylephrine in a dose-related manner. The potencies were in the order of isoprenaline > procaterol >> denopamine. 3. Denopamine-induced dilations were significantly inhibited by 1 nmol betaxolol (a selective beta1-adrenoceptor antagonist), but it was not influenced by 1 nmol ICI 118,551 (a selective beta2-adrenoceptor antagonist). On the other hand, procaterol-induced vasodilations were significantly inhibited by 1 nmol ICI 118,551 but not modified by 10 nmol betaxolol. 4. ACh-induced vasodilations disappeared after intraluminal saponin injection to remove endothelium, but procaterol- and denopamine-induced dilations were not modified by removal of the endothelium. 5. Pretreatment with L-NG-nitroarginine methyl ester (L-NAME) readily inhibited ACh-induced vasodilations. However, neither procaterol- or denopamine-induced vasodilation was modified by L-NAME treatment. 6. From these results, it is concluded that in the rat common carotid arteries (1) there are abundant beta2- and a few beta1-adrenoceptors, and (2) there is no participation of the endothelium-dependent mechanism in beta-adrenoceptor mediated vasodilations.
Chiba
S
S
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Tsukada
M
M
D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015784:Betaxolol / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D004983:Ethanolamines / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010477:Perfusion; D017265:Procaterol / Q000378:metabolism* / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology; D014664:Vasodilation
D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011412:Propanolamines; D011950:Receptors, Cholinergic; D012503:Saponins; C026777:ICI 118551; D007545:Isoproterenol; D015784:Betaxolol; D019331:NG-Nitroarginine Methyl Ester; C037293:denopamine; D017265:Procaterol