La. Fortepiani et al., Pressure natriuresis in nitric oxide-deficient hypertensive rats: Effect of antihypertensive treatments, J AM S NEPH, 10(1), 1999, pp. 21-27
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.