Sodium sensitivity of arterial blood pressure in L-NAME hypertensive but not eNOS knockout mice

The present studies determined the sensitivity of mean arterial pressure (MAP) to sodium intake in endothelial nitric oxide synthase (eNOS) knockout mice, wild-type mice (C56BL/6J), and wild-type mice intravenously administered the nonspecific NOS inhibitor N^G-nitro-l-arginine methyl ester (L-NAME, 8.6 mg/kg/d). Arterial blood pressure was measured from chronically implanted femoral arterial catheters in conscious, freely moving mice. The MAP was unaltered from the low sodium (∼200 μEq/d) intake level of 106 ± 3 mm Hg in wild-type mice when sodium intake was increased to ∼1000 μEq/d (n = 12). Chronic administration of L-NAME to wild-type mice led to a sodium-dependent increase in MAP from 111 ± 7 mm Hg to 124 ± 5 mm Hg when the mice were placed on an elevated sodium intake (n = 7). In contrast to the L-NAME-treated mice, MAP was unaltered in eNOS knockout mice (n = 8) when sodium intake was increased (128 ± 3 mm Hg v 129 ± 5 mm Hg). These experiments demonstrate that eNOS knockout and L-NAME-treated wild-type mice are hypertensive relative to wild-type controls when sodium intake is elevated, but only L-NAME-treated mice exhibited a sodium-sensitive increase in MAP. Therefore, nitric oxide produced by eNOS does not appear to be important in the physiologic adaptation to elevated sodium chloride intake.