Inhibition of Nitric Oxide Synthase 1 Induces Salt-Sensitive Hypertension in Nitric Oxide Synthase 1? Knockout and Wild-Type Mice.

ABSTRACT: We recently showed that ?, ?, and ? splice variants of neuronal nitric oxide synthase (NOS1) expressed in the macula densa and NOS1? accounts for most of the NO generation. We have also demonstrated that the mice with deletion of NOS1 specifically from the macula densa developed salt-sensitive hypertension. However, the global NOS1 knockout (NOS1KO) strain is neither hypertensive nor salt sensitive. This global NOS1KO strain is actually an NOS1?KO model. Consequently, we hypothesized that inhibition of NOS1? in NOS1?KO mice induces salt-sensitive hypertension. NOS1?KO and C57BL/6 wild-type (WT) mice were implanted with telemetry transmitters and divided into 7-nitroindazole (10 mg/kg/d)-treated and nontreated groups. All of the mice were fed a normal salt (0.4% NaCl) diet for 5 days, followed by a high-salt diet (4% NaCl). NO generation by the macula densa was inhibited by >90% in WT and NOS1?KO mice treated with 7-nitroindazole. Glomerular filtration rate in conscious mice was increased by ? 40% after a high-salt diet in both NOS1?KO and WT mice. In response to acute volume expansion, glomerular filtration rate, diuretic and natriuretic response were significantly blunted in the WT and knockout mice treated with 7-nitroindazole. Mean arterial pressure had no significant changes in mice fed a high-salt diet, but increased ? 15 mm Hg similarly in NOS1?KO and WT mice treated with 7-nitroindazole. We conclude that NOS1?, but not NOS1?, plays an important role in control of sodium excretion and hemodynamics in response to either an acute or a chronic salt loading.

SUBMITTER: Wang X 

PROVIDER: S-EPMC4802158 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature