LOCAL MODULATION OF ADRENERGIC RESPONSES IN THE HINDLIMB VASCULATURE OF THE INTACT CONSCIOUS RAF

1. Local modulation of adrenergic responses was examined in the hindli mb vasculature of chronically instrumented intact conscious rats. Spra gue-Dawley rats (n = 22) were instrumented with a Doppler flow probe a round the right common iliac artery, a polyethylene catheter inserted just distal to the flow- probe and a left carotid arterial catheter. 2 . The effects of various concentrations of the alpha(1)-adrenergic rec eptor agonist phenylephrine (0.005-0.075 mu g kg(-1)), the alpha(2)-ad renergic receptor agonist clonidine (0.1-0.7 mu g kg(-1)), and the end ogenous adrenergic receptor agonist adrenaline (0.02-0.08 mu g kg(-1)) , were investigated under control conditions, and in the presence of t he nitric oxide (NO) synthase inhibitor N-omega-nitro-L-arginine methy l ester hydrochoride (L-NAME) (NO-X, 0.2 mg kg(-1)) and the cyclo-oxyg enase inhibitor indomethacin (CO-X, 10 mg Kg(-1)). Results were presen ted as dose-response curves. 3. Heart rate and arterial pressure were not altered by any of the agents because all were locally injected int o the hindlimb vasculature and the selected doses were lower than thos e which elicited systemic responses. 4. Maximal vasoconstrictor respon ses to phenylephrine were enhanced in the presence of NO-X (50 +/- 6%) and CO-X (70 +/- 9%). Maximal vasoconstrictor responses to clonidine were also enhanced in the presence of NO-X (75.3 +/- 4.8%) and CO-X (5 0.8 +/- 5.7%). 5. The responses to adrenaline were biphasic; NO-X sign ificantly attenuated the vasodilator response (87 +/- 6%), and enhance d the vasoconstrictor response (51 +/- 7%). CO-X attenuated the vasoco nstrictor response (71 +/- 6%). 6. These results demonstrate local mod ulation of responses to alpha(1)- and beta-adrenergic receptor agonist s by receptor-mediated dose-dependent release of NO and prostaglandins .