Local modulation of adrenergic responses in the hindlimb vasculature of the intact conscious rat

1. Local modulation of adrenergic responses was examined in the hindlimb vasculature of chronically instrumented intact conscious rats. Sprague-Dawley rats (n = 22) were instrumented with a Doppler flow probe around 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 α₁-adrenergic receptor agonist phenylephrine (0.005-0.075 μg kg^-1), the α₂-adrenergic receptor agonist clonidine (0.1-0.7 μg kg^-1), and the endogenous adrenergic receptor agonist adrenaline (0.02-0.08 μg kg^-1), were investigated under control conditions, and in the presence of the nitric oxide (NO) synthase inhibitor N(ω)-nitro-L-arginane methyl ester hydrochoride (L-NAME) (NO-X, 0.2 mg kg^-1) and the cyclo-oxygenase inhibitor indomethacin (CO-X, 10 mg kg^-1). Results were presented as dose-response curves. 3. Heart rate and arterial pressure were not altered by any of the agents because all were locally injected into the hindlimb vasculature and the selected doses were lower than those which elicited systemic responses. 4. Maximal vasoconstrictor responses 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 (50.6 ± 5.7%). 5. The responses to adrenaline were biphasic; NO-X significantly attenuated the vasodilator response (87 ± 6%), and enhanced the vasoconstrictor response (51 ± 7%). CO-X attenuated the vasoconstrictor response (71 ± 6%). 6. These results demonstrate local modulation of responses to α₁- and β-adrenergic receptor agonists by receptor-mediated dose-dependent release of NO and prostaglandins.