Characterization of the renal microvascular actions of a new dopaminergic (DA1) agonist, YM435

The renal vasculature is known to possess receptors for dopamine. The effects of dopamine and its mimetics on renal hemodynamics, however, have not been fully determined. In the present study, we have characterized the actions of the dopaminergic (DA1) agonist, YM435, on renal microvascular constriction induced by two dissimilar peptide vasoconstrictors, angiotensin II (AII) and endothelin (ET), in the isolated perfused hydronephrotic rat kidney. AII (0.3 nM) constricted afferent (AA) and efferent arterioles (EA) by 30 +/- 2% and 28 +/- 4%, respectively. ET (0.3 nM) preferentially constricted AA (37 +/- 2%) more than EA (18 +/- 2%). The subsequent administration of YM435 reversed the constrictor effects of AII or ET on both AA and EA in a dose-dependent manner. Although YM435 reversed AA and EA vasoconstriction induced by each peptide, the half-maximal inhibitory concentration for YM435 of ET-induced constriction exceeded that of AII (P < .001). Our findings constitute the first demonstration that YM435 is a potent vasodilator in the setting of either AII- or ET-induced AA and EA constriction. These results indicate that DA1 agonists reverse renal microvascular constriction mediated by AII and/or ET, and suggest that both AA and EA constitute the renal microvascular sites of action for DA1 agonists.