Yoshitoki Takagawa

The Role of Nitric Oxide and Kinin on the Renal Water-Sodium Metabolism

Neutral endopeptidase 24.11 (NEP) catabolizes atrial natriuretic peptide (ANP) and kinin, and NEP inhibition results in diuresis and natriuresis. To further investigate the mechanisms of renal effects of NEP inhibitor (NEPI), we observed the role of nitric oxide (NO) together with kinin and ANP. NEPI, UK 73967 or thiorphan and kinin’s receptor antagonist, Hoe 140 (Hoe) were employed, with or without a pretreatment of NO synthase inhibitor, N(1)-monomethyl-L-arginine (L-NMMA) in normal rats. Urinary kinin, NO− 2+NO− 3 (NOx), cGMP, urine volume (UV) and urinary sodium excretion (UNaV) before and after NEPI, and plasma ANP level at the end of experiment, were evaluated. None of the variables changed with vehicle. There were significant increase in kinin, NOx, cGMP, UV and UNaV by NEPI. There were significant positive correlations between Akinin and AUV or ΔUNaV, ΔNOx and ΔUV or UNaV, and ΔcGMP and ΔUNaV. However, there was no difference in plasma ANP between vehicle and NEPI groups. Hoe cancelled the increases of UV and UNaV caused by NEPI. With a pretreatment of L-NMMA, NEPI significantly increased kinin, while cGMP. UV and UNaV did not increase.