On the mechanism of renal vasoconstriction induced by acetylcholine in indomethacin-treated dogs.

Abstract

Renal arterial infusion of acetylcholine (ACh) in control dogs produced a natriuresis and diuresis and an increase in renal plasma flow (RPF) without a change in glomerular filtration rate (GFR) or in renin secretory rate (RSR). In dogs pretreated with indomethacin (Indo), an inhibitor of prostaglandin synthetase, renal arterial infusion of ACh first produced a rise, then a decline in urine flow, sodium excretion (UNaV) and GFR that was accompanied by a progressive fall in RPF and a progressive rise in RSR. The rise in RSR was potentiated by renal arterial infusion of an alpha-adrenergic receptor blocker, phenoxybenzamine (Phenoxy), and attenuated, but not completely abolished, by beta-adrenergic receptor blockade with propranolol (Prop). Chemical denervation with reserpine alone, or in combination with chronic surgical renal denervation, failed to prevent the fall in RPF, GFR and UNaV and the rise in RSR produced by ACh in Indo-treated dogs. Renal arterial infusion of Phenoxy and intravenous infusion of Prop, alone or in combination with renal arterial infusion of an angiotensin II antagonist, saralasin, failed to maintain the vasodilatory, diuretic and natriuretic effects of ACh in Indo-treated dogs. Elimination of endogenous vasopressin by hypophysectomy also failed to prevent the vasoconstriction induced by ACh in Indo-treated dogs. The results suggest that ACh produced renal vasoconstriction in Indo-treated dogs by mechanism(s) other than an increase in renal adrenergetic activity or an increase in the activity of the renin-angiotensin system. The results also suggest that the vasoconstriction was independent of vasopresin.