Pressure natriuresis in nitric oxide-deficient hypertensive rats: Effect of antihypertensive treatments

Chronic inhibition of nitric oxide (NO) synthesis has been shown to result in arterial hypertension and an important blunting of the pressure diuresis and natriuresis response (PDN). The mechanisms mediating these abnormaliti es are not completely understood. In the present study, the role of several antihypertensive drugs to ameliorate these alterations was evaluated. The PDN relationships have been evaluated in rats chronically (8 wk) treated wi th the NO synthesis inhibitor N-G-nitro-L-arginine methyl eater (L-NAME; 40 mg/kg per d in the drinking water). Appropriate groups of rats were simult aneously treated with the angiotensin II receptor blocker candesartan at a low (1.5 mg/kg per d) and high (2.5 mg/kg per d) dose, with the converting enzyme inhibitor captopril (60 mg/kg per d) and with the calcium channel bl ocker verapamil (100 mg/kg per d). Chronic treatment with L-NAME significan tly elevated mean BP (163.6 +/- 6.5 mmHg versus 105.1 +/- 3.6 in controls), reduced GFR and renal blood flow (RBF), and shifted to the right the PDN r esponses. Chronic administration of low-dose candesartan, captopril, or ver apamil prevented the arterial hypertension and improved renal hemodynamics, but these levels were not completely normalized. High-dose administration also improved renal hemodynamics but induced reduced BP below the levels of control animals. Despite the normalization of the elevated BP, the PDN res ponses of these hypertensive treated groups were not normalized, and the sl opes of the respective diuretic or natriuretic responses were very similar to those of the hypertensive untreated rats. The results indicate that inte rruption or blockade of the renin-angiotensin system and calcium channel bl ockade are effective treatments for the NO-deficient arterial hypertension and renal vasoconstriction. However, the PDN responses are not normalized, and this finding suggests that the antihypertensive treatment is not enough to overcome the renal alterations associated with the chronic deficiency o f NO.