Pressure Natriuresis in AT2Receptor–Deficient Mice with L-NAME Hypertension

Abstract

ABSTRACT. AT2receptor-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 ± 2versus108 ± 4 mmHg). This difference occurred even though L-NAME–treated AT2+/+ mice had a greater sodium excretion than AT2−/− mice (10.9 ± 0.5versus8.0 ± 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 ± 0.08versus1.21 ± 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 (FENa) and water (FEH2O) curves were shifted more strongly to the right by L-NAME in AT2−/− mice than in AT2+/+ mice. AT1receptor blocker treatment lowered BP in both L-NAME–treated strains to basal values. It is concluded that the AT1receptor 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: luft@fvk-berlin.de