NOS1 Knockout mice exhibit delayed Na excretion following a high salt challenge

Previous studies have shown that nitric oxide (NO) inhibits Na transport and acute infusion of a NO synthase 1 (NOS1) inhibitor into the renal medulla results in hypertension. The purpose of this study is to test the hypothesis that NOS1 facilitates the elimination of an acute salt load. Wild type (WT) and NOS1 knockout (KO) mice were implanted with telemetry transmitters to monitor mean arterial pressure (MAP). Both strains of mice were fed a Na deficient diet and placed in metabolic cages to monitor Na excretion. Following a 2 day baseline period, mice were given 90 μEq Na in 150 mg of chocolate pudding that was consumed in 10 minutes. Urine was collected in three, 12 hr periods following the Na challenge. Baseline MAP in WT mice was 110 ± 9 mmHg, increased by 21 ± 2 mmHg within 2 hrs of the Na challenge and remained elevated for a period of 6 hrs (n=4). NOS1KO mice baseline MAP was 105 ± 6 mmHg and exhibited similar increases of 19 ± 2 mmHg, although it was delayed to 4 hrs after the Na challenge and returned to baseline levels within 2 hrs (n=4). WT mice excreted significantly higher Na within the first 12 hrs, 85.5 ± 4% (n=4, p<.04) while the NOS1KO excreted only 11.3 ± 1.8% (n=4) during the same period. Furthermore, NOS1KO excreted only 45.3 ± 3% over 36 hrs. Urinary endothelin (ET‐1) excretion was similarly increased between strains by the Na challenge, 7.9 ± 2.8 fmol/h (WT, n=4) and 10.7 ± 5 fmol/h (KO, n=4), thus indicating that NOS1 does not play a role in the control of ET‐1 excretion. These findings indicate NOS1 influences the blood pressure response to high salt and participates in the excretion of an acute salt load either through a renal or extra‐renal mechanism. (NIH HL60653; HL66993)