Evidence that specific dopamine-1 receptor activation is involved in dopamine-induced renin release

Abstract

Direct effects of dopamine on renin release were examined using static incubations and perifusions of rat renal cortical slices. Dopamine (10-5 M) significantly stimulated renin release compared with control. To determine which receptors are involved in dopamine-elicited renin release, studies were performed with specific dopamine-1 and dopamine-2 receptor agonists and antagonists, as well as with α- and β-adrenergic antagonists. Fenoldopam, a dopamine-1 receptor agonist, dose dependently stimulated renin secretion both in static incubations and perifusions; whereas quinpriole (10-7-10-5 M), a dopamine-2 receptor agonist, was ineffective. Phentolamine (10-4 M), an α-adrenergic antagonist, did not alter dopamine- or fenoldopam-induced renin release. Similarly, propranolol, a β-blocker, did not interfere with the renin stimulation of dopamine (10-5 M) or fenoldopam (10-6 M) in incubations or perifusion experiments; whereas propranolol significantly blocked isoproterenol action. SCH 23390 (10-5 M), a specific dopamine-1 antagonist, blocked dopamine- and fenoldopam-induced renin. In contrast, pimozide, a dopamine-2 receptor antagonist, was ineffective. These studies indicate that dopamine is a direct renin secretogogue, and its effects seem to be mediated by specific dopamine-1 receptor activation, as neither α- nor β-adrenergic blockers nor dopamine-2 receptor antagonists altered dopamine actions. The results suggest that dopamine produced locally in the kidney may stimulate renin secretion directly by dopamine-1 receptor activation.