Propranolol stereoselectively inhibits alpha-adrenoceptor-mediated vasoconstriction in mesenteric arterial beds of rats.
1. The optical isomers of propranolol were compared for their effects on pressor responses to adrenergic and non-adrenergic vasoconstrictors in mesenteric arterial beds of rats. 2. R(+)-propranolol (10(-7)-10(-5) M) had no effect on vessel preparations stimulated with noradrenaline, methoxamine, or arginine-vasopressin. 3. S(-)-propranolol 10(-7) M did not alter pressor responses to noradrenaline. However, S(-)-propranolol 10(-6) and 10(-5) M inhibited vasoconstriction induced by noradrenaline. This effect was similar in the presence of indomethacin 3 x 10(-6) M. 4. S(-)-propranolol 10(-5) M also inhibited vasoconstriction induced by methoxamine, shifting the dose-response curves to the right, but did not affect pressor responses to arginine-vasopressin. 5. Schild analysis for equilibrium vasoconstrictor responses to methoxamine indicated stereoselective competitive alpha-adrenoceptor antagonism by propranolol. 6. These data suggest selective inhibition of alpha-adrenoceptor-mediated vasoconstriction by S(-)-propranolol at higher concentrations by competitive alpha-adrenoceptor antagonism.
Stauber
R E
RE
Department of Medicine, Karl Franzens University, Graz, Austria.
Heinemann
A
A
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D008638:Mesenteric Arteries; D008729:Methoxamine / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors*
D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D014662:Vasoconstrictor Agents; D011433:Propranolol; D008729:Methoxamine; D009638:Norepinephrine