Role of atrial natriuretic peptide in mediating the blood pressure-independent natriuresis elicited by systemic inhibition of nitric oxide.

Abstract

While it is clearly recognized that increased intrarenal nitric oxide (NO) levels elicit natriuresis, confounding data showing that systemic nitric oxide synthase inhibition (NOSi) also increases sodium excretion (UNaV) poses a conundrum. This response has been attributed to the associated increases in arterial pressure (AP); however, the increases in AP and in UNaV are temporally dissociated. The changes in regional renal haemodynamics induced by NOSi could also contribute to the alterations of UNaV. To evaluate the roles of AP and non-AP mechanisms mediating the natriuresis, N ω-nitro-l-arginine methyl ester hydrochloride (L-NAME) was infused i.v. at doses ranging from 5 to 50 μg/kg/min in anaesthetized rats. UNaV, perfusion of the cortex (cortical blood flow, CBF) and medulla (medullary blood flow, MBF) with laser-Doppler flowmetry and glomerular filtration rate (GFR) were measured. UNaV increased from 0.6 ± 0.2 to 1.6 ± 0.1 μmol/kg/min (P < 0.05) with the lower nonpressor doses. With the higher doses, AP increased from 116 ± 4 to 122 ± 4 mmHg and UNaV increased from 1.1 ± 0.3 to 3.3 ± 0.7 μmol/min/g (P < 0.002). UNaV increased similarly in a group where renal AP was maintained at baseline levels. The associated reductions in CBF (17 ± 5 and 38 ± 5 %) and MBF (27 ± 6 and 52 ± 6 %) would be expected to attenuate rather than contribute to the natriuresis. Plasma atrial natriuretic peptide (ANP) concentrations increased significantly following NOSi. Anantin, a natriuretic peptide receptor-A blocker, prevented or reversed the L-NAME-induced natriuresis without altering the L-NAME-induced changes in AP or CBF. The results indicate that increased ANP and related natriuretic peptides mediate the AP-independent natriuresis, at least partly, elicited by systemic L-NAME infusion and help resolve the conundrum of natriuresis during systemic NOSi.