EFFECTS OF HYDRALAZINE ON CONTRACTILE RESPONSES TO ALPHA(1) AND ALPHA(2)-ADRENOCEPTOR AGONISTS IN ISOLATED RUBBED RAT AORTA

1. Effects of hydralazine on contractile responses to noradrenaline (a n alpha(1)- and alpha(2)-adrenoceptor agonist) to phenylephrine and me thoxamine (both selective alpha(1)-adrenoceptor agonists) and to cloni dine and BHT-920 (both relatively selective alpha(2)-adrenoceptor agon ists) were examined in isolated rat aorta deprived of endothelium. Hyd ralazine (1 mM) produced a rightward shift with depression of the maxi mal tension of the concentration-response curves for all the agonists tested. The effects on curves for clonidine and BHT-920 (partial agoni sts) were greater than on curves for noradrenaline, phenylephrine and methoxamine (full agonists). 2. The inhibitory effect of prazosin (pA( 2), about 10) was much greater than that of yohimbine (pA(2), about 7) for all the agonists. 3. In tissues pretreated with phenoxybenzamine, hydralazine (1 mM) inhibited the residual response to all the agonist s. The inhibitory effect on residual response to full agonists was sim ilar to that observed on response to partial agonists in tissues not t reated with phenoxybenzamine. 4. The relationship between maximal resp onse and percentage receptor occupancy was nonlinear for full agonists , but near-linear for partial agonists. 5. These results indicate that the responses induced by noradrenaline, phenylephrine, methoxamine, c lonidine and BHT-920 in the rat aorta are due to the activation of alp ha(1)-adrenoceptors and confirm the vasorelaxant action of hydralazine . 6. These results also suggest that the differential effects of hydra lazine on the responses to alpha-adrenoceptor agonists may be due to d ifferences in the amount of receptor reserve available in this blood v essel for full agonists (noradrenaline, phenylephrine or methoxamine) and partial agonists (clonidine or BHT-920).