Reinvestigation of the tonic natriuretic action of intrarenal dopamine: comparison of two variants of salt-dependent hypertension and spontaneously hypertensive rats.

Abstract

The intrarenal dopamine system has been thoroughly investigated at all levels, especially its role in salt-dependent and other forms of hypertension. However, the evidence regarding dopamine's tonic influence on renal tubular transport of sodium remains equivocal. We reinvestigated its tonic influence on sodium excretion and systemic and renal haemodynamics. Early effects of dopamine D1 receptor blockade using 90-min Schering 23390 (SCH) infusion were examined in anaesthetized rats on 7days' high salt diet (HS), early uninephrectomized rats on 14days' HS diet, drinking 1% saline (HS/UNX), and in spontaneously hypertensive rats (SHR). In the HS group (baseline BP ~133mmHg) renal intracortical SCH promptly decreased sodium, water and total solute excretion (UNa V, V, Uosm V), with significant difference from the solvent-infused group. BP and renal artery blood flow (RBF, Transonic probe) did not change. In HS/UNX model (baseline BP ~150mmHg), characterized by hypertrophy of the remaining kidney, the excretion parameters only tended to decrease whereas SCH induced an ~20% fall in RBF. In SHR (BP ~180mmHg), UNa V and V tended to increase in solvent-infused rats; this increasing tendency was abolished by SCH infusion. During experiments the renal vascular resistance increased significantly in SCH- and solvent-infused SHR. Despite some contradictory findings regarding the genuine tonic control of renal excretion by intrarenal dopamine, our results clearly support such role in rats on HS diet and in SHR, the model resembling human essential hypertension. The observations strengthen the experimental basis and the rationale for targeting the intrarenal dopamine system in attempts to combat arterial hypertension.