RENAL VASODILATATION BY DOPEXAMINE AND FENOLDOPAM DUE TO ALPHA(1)-ADRENOCEPTOR BLOCKADE

1 The renal vascular responses of the rat isolated perfused kidney to the dopamine D-1-receptor agonists, dopexamine and fenoldopam, were ex amined. 2 Both kidneys were perfused in situ at constant flow rate (11 ml min(-1)) with Krebs-bicarbonate solution at 37 degrees C. The perf usion pressure was monitored and to enable vasodilator responses to be measured, the resting perfusion pressure was raised by infusing norad renaline (6 x 10(-9) M). 3 Dose-related vasodilator responses to bolus doses of dopexamine and fenoldopam were obtained. However, these were not antagonized by the D-1-receptor antagonist, SCH 23390, indicating that D-1-receptors were not involved. 4 Bolus doses of the alpha(1)-a drenoceptor antagonist, prazosin, caused similar dose-related vasodila tor responses indicating the possibility that alpha(1)-adrenoceptor bl ocking properties of dopexamine and fenoldopam were responsible for th e vasodilatation. 5 alpha-Adrenoceptor blockade by dopexamine and feno ldopam was confirmed by the parallel displacement of dose-response cur ves for the vasopressor responses to noradrenaline. pA(2) values were determined by Schild analysis for dopexamine, fenoldopam and prazosin antagonism of noradrenaline in the presence of neuronal (cocaine, 10(- 5) M) and extraneuronal uptake blockade (metanephrine, 10(-5) M). The values were 6.23, 6.02 and 8.91, respectively. Schild plot slopes of u nity were obtained for dopexamine and fenoldopam indicating competitiv e antagonism. A slope of greater than unity for prazosin may be explai ned by the lack of equilibrium conditions associated with bolus doses of noradrenaline, the responses of which are affected more by the high affinity antagonist, prazosin, than the two lower affinity antagonist s. 6 This study has demonstrated that renal vasodilator responses to t he D-1-receptor agonists, dopexamine and fenoldopam, are due to a brie f antagonism of the alpha-adrenoceptor-mediated vasoconstriction induc ed by noradrenaline. This presumably masks any direct D-1-receptor-med iated vasodilatation.