The regulation of regional hemodynamics by alpha-1 adrenoceptor subtypes in the conscious rat

The role of alpha-1 adrenoceptors sensitive and resistant to chloroethylclonidine (CEC) in the regulation of peripheral hemodynamics in the conscious rat has been examined. CEC treatment (15, 25 or 30 mg/kg i.p.) resulted in a sustained decrease in systemic arterial blood pressure and heart rate. These same concentrations reduced, but did not eliminate, [3H]prazosin binding sites in vascular smooth muscle homogenates. The effect of CEC administration on blood flow and regional vascular resistance was assessed using pulsed-Doppler flow probes implanted around the superior mesenteric and iliac arteries. CEC treatment resulted in a significant decrease in mesenteric and hindlimb resistance. Prazosin (3 or 5 mg/kg) reduced systemic arterial blood pressure and vascular resistance to a greater degree than did CEC. The dose-response curve for phenylephrine-induced increases in mesenteric or hindlimb vascular resistance was shifted only 2- to 10-fold to the right by CEC. Prazosin, by contrast, shifted the phenylephrine dose-response curve over 100-fold to the right. These data indicate that multiple alpha-1 adrenoceptor subtypes, both CEC sensitive and insensitive, participate in the regulation of blood flow to the gut and the hindlimb. Finally, CEC sensitive sites do not appear to play as prominent a role as insensitive sites in mediating the pressor response to phenylephrine.