Contrasting effect of substance P on renal function and dopamine excretion in hydropaenic and volume expanded dogs

1. Substance P (SP) and dopaminergic nerves have been described in the kidney. In the brain, SP increases dopamine production. In the kidney, SP increases sodium excretion. 2. Intrarenal dopamine acts as an endogenous natriuretic hormone. It is possible that dopamine could mediate the natriuretic effect of SP. 3. We therefore studied the effect of the intrarenal arterial infusion of SP (0.1, 1.0, 10 ng kg body wt-1 min-1) on mean arterial pressure (MAP), renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (V), absolute (UNaV) and fractional (FENa) sodium excretion as well as dopamine and noradrenaline excretion in dogs. Since dopamine is not natriuretic in hydropaenic states, studies were performed during hydropaenic and saline loaded states. 4. During hydropaenia, SP increased RBF, GFR, and V in a dose-related fashion but did not alter UNaV or FENa. Urinary noradrenaline was not affected but urinary dopamine decreased with increasing doses of SP. MAP was not affected. 5. During saline loading, SP increased RBF, GFR, V, UNaV, and FENa in a dose-related fashion. Both urinary noradrenaline and urinary dopamine increased. The fractional excretion of sodium correlated with dopamine but not noradrenaline excretion. MAP was not affected. 6. The renal haemodynamic and functional effects of SP may be mediated by SP-associated increases in urinary dopamine.