THE REGULATION OF REGIONAL HEMODYNAMICS BY ALPHA-1-ADRENOCEPTOR SUBTYPES IN THE CONSCIOUS RAT

The role of alpha-1 adrenoceptors sensitive and resistant to chloroeth ylclonidine (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 pressur e and heart rate. These same concentrations reduced, but did not elimi nate, [H-3]prazosin binding sites in vascular smooth muscle homogenate s. The effect of CEC administration on blood flow and regional vascula r resistance was assessed using pulsed-Doppler flow probes implanted a round the superior mesenteric and iliac arteries. CEC treatment result ed in a significant decrease in mesenteric and hindlimb resistance. Pr azosin (3 or 5 mg/kg) reduced systemic arterial blood pressure and vas cular resistance to a greater degree than did CEC. The dose-response c urve for phenylephrine-induced increases in mesenteric or hindlimb vas cular resistance was shifted only 2- to 10-fold to the right by CEC. P razosin, by contrast, shifted the phenylephrine dose-response curve ov er 100-fold to the right. These data indicate that multiple alpha-1 ad renoceptor subtypes, both CEC sensitive and insensitive, participate i n the regulation of blood flow to the gut and the hindlimb. Finally, C EC sensitive sites do not appear to play as prominent a role as insens itive sites in mediating the pressor response to phenylephrine.