Role of neuronal nitric oxide synthase in response to hypertonic saline loading in rats

Abstract

This study analyses the influence of neuronal nitric oxide synthase (nNOS) blockade with 7-nitroindazole (7NI) on the haemodynamic and renal response to a hypertonic saline load (HSL). We also evaluated the effects of non-specific NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). The following groups were used: controls, rats treated with 7NI at 0.5 or 5 mg kg(-1), and rats treated with L-NAME at 0.5 or 5 mg kg(-1). A further five groups received an isotonic saline load (ISL). Mean arterial pressure (MAP) was significantly increased in control rats after HSL. MAP was further increased in both 7NI-treated groups, and the L-NAME groups showed marked dose-related pressor responses. During ISL, MAP was only significantly increased in the group treated with 5 mg kg(-1) of L-NAME. The pressure-natriuresis relationship during the experimental period after the HSL was reduced in the 7NI group treated with 5 mg kg(-1) and severely attenuated in both L-NAME groups. The increase in plasma sodium was significantly greater after the HSL in both 7NI groups and both L-NAME groups compared with controls. The present results suggest that nNOS and other NOS isozymes play a counter-regulatory role in the pressor response to HSL. Moreover, the blockade of nNOS with the higher dose of 7NI produces a blunted pressure-natriuresis relationship in response to the HSL. Finally, it is concluded that nNOS participates in the homeostatic cardiovascular and renal response to hypertonic saline loading by attenuating the blood pressure increase and hypernatremia, and facilitating natriuresis.