Malate reduced blood pressure and exerted differential effects on renal hemodynamics; role of the nitric oxide system and renal epithelial sodium channels (ENaC)

Malate regulates blood pressure via nitric oxide production in salt-sensitive rats, a genetic model of hypertension. This study investigated the possible contributions of malate to blood pressure regulation and renal haemody-namics in normotensive rats. Malate (0.1, 0.3 and 1 mu g/kg, iv) was injected into rats or L-nitro-arginine methyl ester (L-NAME)-treated rats and mean arterial blood pressure (MABP), cortical blood flow (CBF), and medullary blood flow (MBF), was measured. The clearance study involved infusion of malate at 0.1 mu g/kg/h into rats, and MABP, CBF, MBF, glomerular filtration rate (GFR), urine volume (UV) and sodium output (UNaV) were deter-mined. Mechanistic studies to evaluate the role of renal sodium channels involved the treatment with malate (600 mg/kg, po), amiloride (2.5 mg/kg, po) or hydrochlorothiazide (HCTZ) (10 mg/kg, po), and UV and UNaV were determined. Malate elicited significant peak reductions in MABP (124 +/- 6.5 vs 105 +/- 3.1 mmHg) at 0.1 mu g/ kg), CBF (231 +/- 18.5 vs 205 +/- 10.9 PU). L-NAME did not reverse the effect of malate on MABP but tended to blunt the effect on CBF (40%) and MBF (87%) at 0.3 mu g/kg. Infusion of malate reduced MABP, CBF, and MBF in a time-dependent manner (p<0.05). Malate exerted a three-fold decrease in GFR in a time-related fashion (p<0.05) as well as increased UV. UNaV increased by 86% in malate-treated-amiloride rats (p<0.05). These data indicate that malate modulates blood pressure and exerts vascular and tubular effects on renal function that may involve epithelial sodium channels (ENaC).