EFFECT OF THE DOPAMINE-D2 RECEPTOR AGONIST QUINPIROLE ON RENAL SYMPATHETIC-NERVE ACTIVITY AND RENAL NOREPINEPHRINE SPILLOVER IN ANESTHETIZED RABBITS

Cardiovascular and sympathetic nervous system effects of the dopamine D2 receptor-selective agonist quinpirole were studied in anesthetized rabbits. Sodium nitroprusside was administered for comparison. The animals received a tracer infusion of [H-3] norepinephrine i.v. Arterial and renal venous concentrations of endogenous norepinephrine and epinephrine and [H-3]norepinephrine, the firing rate of the renal sympathetic nerves and renal blood flow were determined. Quinpirole (100 mug kg-1 + 5 mug kg-1 min-1 i.v.) lowered blood pressure and renal vascular resistance. The firing rate of the renal sympathetic nerves was increased, but there was no reflex tachycardia. Despite the increase in renal sympathetic firing, the renal spillover of norepinephrine into blood was decreased. The increase in total body norepinephrine spillover during quinpirole-induced hypotension was less than expected from baroreflex activation. Effects of quinpirole were antagonized by domperidone (1000 mug kg-1 + 200 mug kg-1 h-1). The distinguishing feature of this study is the simultaneous measurement of sympathetic firing and norepinephrine spillover in the same organ, the kidney, under conditions of intact sympathetic impulse traffic. Quinpirole activated presynaptic D2 receptors and thus reduced the released norepinephrine per action potential. Consequences of the presynaptic inhibition were reductions of blood pressure and renal vascular resistance and absence of reflex tachycardia.