Evaluation of the role of alpha-1 and alpha-2 adrenoceptors in the maintenance of neurogenic tone to the hindlimb vasculature.

The location of two distinct subtypes of alpha adrenoceptors on blood vessels is now well established. The present study was designed to assess the relative contribution of alpha-1 and alpha-2 adrenoceptors to the maintenance of sympathetic vasoconstrictor tone to the canine hindlimb. Bilateral hindlimb perfusion was carried out at controlled flow rates where one of the hindlimbs was neurally intact and the other limb was denervated surgically. Vascular resistances in the hindlimbs were evaluated by pressure-flow curves which were constructed by recording perfusion pressures at various flow levels. Administration of alpha-1 adrenoceptor antagonist, prazosin (50 micrograms/kg), which selectively inhibited the hindlimb vasoconstrictor effect of phenylephrine but not of B-HT 933, produced a significant decrease in the hindlimb vascular resistance in the innervated limb. This was reflected in a decrease in perfusion pressure and a downward shift of the pressure-flow curve of 30% from control. No changes in resistance occurred in the denervated limb. The alpha-2 adrenoceptor antagonist, yohimbine (100 micrograms/kg), which selectively antagonized vasoconstriction to B-HT 933 but not to phenylephrine, further decreased by 27% hindlimb vascular resistance in the innervated limb when given to the same group of prazosin-treated animals. The magnitude of the decrease in vascular resistance produced by yohimbine (27%) was similar to that caused by prazosin (30%). The vascular resistance in the innervated limb was now similar to that in the denervated limb after prazosin and yohimbine. Phentolamine, when administered after prazosin and yohimbine, did not produce any changes in the hindlimb vascular resistance in these dogs.(ABSTRACT TRUNCATED AT 250 WORDS)