Dissociation of renal vasodilator and natriuretic effects of dopamine during sulpiride infusion in normal man

Summary

The effect of sulpiride on dopamine-induced changes in renal function in man has been investigated. Dopamine dose-response studies were performed in 7 healthy volunteers before and after sulpiride 200 mg i. v. The same investigations were performed in 15 healthy volunteers after pretreatment with the selective alpha-1-adrenoceptor antagonist prazosin (n=7) and the non-selective alpha-adrenoceptor-blocker phentolamine (n=8).

Infusion of dopamine 0.25 to 8 μg·kg⁻¹·min⁻¹ resulted in a dose-dependent increase in effective renal plasma flow (ERPF) and glomerular filtration rate (GFR), and a fall in filtration fraction (FF) in 7 normal volunteers. Sulpiride had no effect on base-line ERPF or GFR and did not influence the dopamine-induced renal vasodilatation in those volunteers. It did cause a fall in the fractional sodium excretion (FENa⁺%) from 1.7 to 1.38, and shifted the dose-response curve of the natriuretic response to a subsequent infusion of dopamine. Sulpiride enhanced the fall in diastolic blood pressure during infusion of dopamine.

In 7 other volunteers pretreated with prazosin, sulpiride did not influence base-line ERPF, GFR or FF or their response to dopamine, but the sodium excretion fell markedly (FENa⁺% changed from 1.13 to 0.63). Administration of sulpiride to 8 volunteers after phentolamine pretreatment 20 mg·h⁻¹ i.v. in the first hour followed by 10 mg·h⁻¹ i.v. resulted in a fall in sodium excretion (FENa⁺% from 1.09 to 0.53) without affecting ERPF or FF, and it did not affect the dose-response curve in the subsequent DA infusion. Both after prazosin pretreatment and during phentolamine infusion the usual natriuretic response to dopamine was completely absent, while phentolamine alone did not influence base-line values of sodium excretion or of ERPF, GFR and FF.

Overall, in normal men sulpiride did not antagonise the dopamine-induced renal vasodilatation. This was not due to a presumed additional alpha-antagonist activity of sulpiride. Its effect on base-line sodium excretion and dopamine-induced natriuresis did not appear to be dependent on renal haemodynamics and may be the consequence of inhibition of a direct proximal tubular effect of dopamine.