| First Author | Lu Y | Year | 2016 |
| Journal | J Am Soc Nephrol | Volume | 27 |
| Issue | 8 | Pages | 2346-56 |
| PubMed ID | 26647426 | Mgi Jnum | J:283147 |
| Mgi Id | MGI:6377927 | Doi | 10.1681/ASN.2015050515 |
| Citation | Lu Y, et al. (2016) Macula Densa Nitric Oxide Synthase 1beta Protects against Salt-Sensitive Hypertension. J Am Soc Nephrol 27(8):2346-56 |
| abstractText | Nitric oxide (NO) is an important negative modulator of tubuloglomerular feedback responsiveness. We recently found that macula densa expresses alpha-, beta-, and gamma-splice variants of neuronal nitric oxide synthase 1 (NOS1), and NOS1beta expression in the macula densa increases on a high-salt diet. This study tested whether upregulation of NOS1beta expression in the macula densa affects sodium excretion and salt-sensitive hypertension by decreasing tubuloglomerular feedback responsiveness. Expression levels of NOS1beta mRNA and protein were 30- and five-fold higher, respectively, than those of NOS1alpha in the renal cortex of C57BL/6 mice. Furthermore, macula densa NO production was similar in the isolated perfused juxtaglomerular apparatus of wild-type (WT) and nitric oxide synthase 1alpha-knockout (NOS1alphaKO) mice. Compared with control mice, mice with macula densa-specific knockout of all nitric oxide synthase 1 isoforms (MD-NOS1KO) had a significantly enhanced tubuloglomerular feedback response and after acute volume expansion, significantly reduced GFR, urine flow, and sodium excretion. Mean arterial pressure increased significantly in MD-NOS1KO mice (P<0.01) but not NOS1flox/flox mice fed a high-salt diet. After infusion of angiotensin II, mean arterial pressure increased by 61.6 mmHg in MD-NOS1KO mice versus 32.0 mmHg in WT mice (P<0.01) fed a high-salt diet. These results indicate that NOS1beta is a primary NOS1 isoform expressed in the macula densa and regulates the tubuloglomerular feedback response, the natriuretic response to acute volume expansion, and the development of salt-sensitive hypertension. These findings show a novel mechanism for salt sensitivity of BP and the significance of tubuloglomerular feedback response in long-term control of sodium excretion and BP. |
