The α1-adrenergic receptor not the DA1-dopaminergic receptor mediates cyclosporine–SKF38393 renovascular interaction

Abstract

In this study, we investigated the effect of acute exposure to cyclosporine A (CyA) on renal vasodilations evoked by the DA1 dopaminergic agonist SKF38393 and whether dopamine DA1 receptors are directly involved in the interaction. Changes evoked by CyA in SKF38393 vasodilations were evaluated in phenylephrine-preconstricted isolated perfused rat kidneys in the absence and presence of SCH23390, a DA1 receptor antagonist. SKF38393 (3 × 10–8 to 3 × 10–6 mol) produced dose-dependent reductions in the renal perfusion pressure that were significantly attenuated in tissues pretreated with SCH23390 or CyA. Unlike SKF38393, the vasodilatory action of sodium nitroprusside, a nitrovasodilator, was not altered by CyA. The attenuating effect of CyA on SKF38393 vasodilations was preserved in preparations pretreated with SCH23390, suggesting that sites other than DA1 receptors may be involved in CyA–SKF38393 interaction. The study was then extended to investigate the possible involvement of renal α1-adrenoceptors in the interaction. Blockade of α1-adrenoceptors by prazosin (30 nmol/L) significantly reduced the vasodilatory effect of SKF38393 and virtually abolished the CyA-induced attenuation of SKF38393 responses. Further, CyA failed to alter SKF38393 vasodilations when the renal tone was raised with prostaglandin F2α (PGF2α), a vasoconstrictor whose effect is independent of α1-adenoceptors. Together, these findings support earlier reports that both DA1 and α1-receptors mediate the renal vasodilatory action of SKF38393 and suggest that CyA interacts selectively with the α1-receptor component to compromise SKF38393 responses.