| First Author | Wang X | Year | 2016 |
| Journal | Hypertension | Volume | 67 |
| Issue | 4 | Pages | 792-9 |
| PubMed ID | 26883268 | Mgi Jnum | J:280765 |
| Mgi Id | MGI:6369573 | Doi | 10.1161/HYPERTENSIONAHA.115.07032 |
| Citation | Wang X, et al. (2016) Inhibition of Nitric Oxide Synthase 1 Induces Salt-Sensitive Hypertension in Nitric Oxide Synthase 1alpha Knockout and Wild-Type Mice. Hypertension 67(4):792-9 |
| abstractText | We recently showed that alpha, beta, and gamma splice variants of neuronal nitric oxide synthase (NOS1) expressed in the macula densa and NOS1beta 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 NOS1alphaKO model. Consequently, we hypothesized that inhibition of NOS1beta in NOS1alphaKO mice induces salt-sensitive hypertension. NOS1alphaKO 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 NOS1alphaKO mice treated with 7-nitroindazole. Glomerular filtration rate in conscious mice was increased by approximately 40% after a high-salt diet in both NOS1alphaKO 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 approximately 15 mm Hg similarly in NOS1alphaKO and WT mice treated with 7-nitroindazole. We conclude that NOS1beta, but not NOS1alpha, plays an important role in control of sodium excretion and hemodynamics in response to either an acute or a chronic salt loading. |
