Pressure Natriuresis in AT₂ Receptor–Deficient Mice with L-NAME Hypertension

Abstract

ABSTRACT. AT₂ receptor-disrupted (AT₂ −/−) mice provide a unique opportunity to investigate the cardiovascular and BP-related effects of NO depletion. This study compared the pressure-diuresis-natriuresis relationship in (AT₂ −/−) and wild-type (AT₂ +/+) mice after treating the animals with L-NAME (130 mg/kg body wt per day) for 1 wk. L-NAME increased mean arterial pressure (MAP) more in AT₂ −/− than in AT₂ +/+ mice (118 ± 2 versus 108 ± 4 mmHg). This difference occurred even though L-NAME–treated AT₂ +/+ mice had a greater sodium excretion than AT₂ −/− mice (10.9 ± 0.5 versus 8.0 ± 1.0 μmol/h). The pressure-natriuresis relationship in conscious AT₂ −/− mice was shifted rightward compared with controls. RBF was decreased in AT₂ −/− compared with AT₂ +/+ mice. L-NAME decreased RBF in these mice further from 4.08 ± 0.43 to 2.79 ± 0.15 ml/min per g of kidney wt. GFR was not significantly different between AT₂ +/+ and AT₂ −/− mice (1.09 ± 0.08 versus 1.21 ± 0.09 ml/min per g of kidney wt). L-NAME reduced GFR in AT₂ −/− to 0.87 ± 0.07 ml/min per g of kidney wt. Fractional sodium (FE_Na) and water (FE_H2O) curves were shifted more strongly to the right by L-NAME in AT₂ −/− mice than in AT₂ +/+ mice. AT₁ receptor blocker treatment lowered BP in both L-NAME–treated strains to basal values. It is concluded that the AT₁ receptor plays a key role in the impaired renal sodium and water excretion induced by NO synthesis blockade. Changes in RBF, GFR, and tubular sodium and water reabsorption are involved and may be also responsible for the greater BP increase in L-NAME–treated AT₂ −/− mice. E-mail: [email protected]