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 haemodynamics in normotensive rats. Malate (0.1, 0.3 and 1 μg/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 μg/kg/h into rats, and MABP, CBF, MBF, glomerular filtration rate (GFR), urine volume (UV) and sodium output (UNaV) were determined. 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 μg/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 μg/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). Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Osaze Edosuyi, Ayobami Adesuyi, Myung Choi, Ighodaro Igbe, Adebayo Oyekan. Malate reduced blood pressure and exerted differential effects on renal hemodynamics; role of the nitric oxide system and renal epithelial sodium channels (ENaC). European journal of pharmacology. 2023 Jan 05;938:175441

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PMID: 36463945

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