Specific alpha-adrenergic receptor desensitization in vascular smooth muscle.

Specific desensitization of vascular tissue to norepinephrine was studied using an open-ring-type strip preparation of rabbit aorta. Aortae were taken from untreated, reserpine-pretreated (0.1 mg/kg/day; 3, 5, or 7 days) and 6-hydroxydropamine-pretreated (50 mg/kg; 3 or 7 days before sacrifice) rabbits. Aortic strips from the pretreated rabbits were supersensitive to norepinephrine. Subsequent to obtaining the first dose-response curve for norepinephrine, aortic strips were less sensitive to norepinephrine. It was found that desensitization to norepinephrine occurred following 10 min preincubation with 10(-6)m norepinephrine, and 20 min preincubation with 10(-7)m norepinephrine. The desensitization of supersensitive strips was significantly greater than in controls. Dopamine and isoproterenol desensitized both untreated and pretreated strips to norepinephrine. Phenylephrine desensitized strips to norepinephrine from 6-hydroxydopamine-pretreated rabbits. Acetylcholine and potassium did not desensitize strips to norepinephrine; however, acetylcholine desensitized strips to acetylcholine. It is concluded from these studies that norepinephrine desensitization in a specific alpha-adrenergic-related event.