Effect of endothelin blockade on pressure natriuresis in nitric oxide-deficient hypertensive rats

Objective Chronic inhibition of nitric oxide synthesis has been shown to ca use arterial hypertension and an important blunting of the pressure diuresi s and natriuresis response. The mechanisms mediating these abnormalities ar e not completely established. We therefore studied the effects of endotheli n on these alterations. Materials and methods Pressure diuretic and natriuretic relationships were evaluated in rats treated chronically (3 weeks) with the nitric oxide synth esis inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg per day), alone or in combination with bosentan sodium salt (acute treatment: 1 0 mg/kg, intravenously; chronic treatment: 10 mg/kg per day). Results Chronic treatment with L-NAME significantly elevated mean arterial pressure (143.7 +/- 2.8 mmHg versus 102.8 +/- 1.6 in controls), reduced the glomerular filtration rate and renal blood flow and shifted the pressure d iuretic and natriuretic responses to the right. Treatment with bosentan, ei ther acute or chronically, did not attenuate the arterial hypertension of t he L-NAME-treated rats but normalized the glomerular filtration rate and re nal blood flow. In spite of the normalization of renal hemodynamics, the pr essure diuretic and natriuretic responses of the bosentan-treated groups we re not normalized, although chronic bosentan significantly improved the pre ssure natriuretic response. Conclusions These results indicate that endothelin participates in the rena l hemodynamic and excretory alterations that follow chronic inhibition of n itric oxide synthesis. However, the arterial hypertension is not mediated b y endothelin activation. (C) Lippincott Williams & Wilkins.