Journal of Clinical & Experimental Pathology
Open Access

Abstract

Tubuloglomerular feedback (TGF) response operates at the level of juxtaglomerular apparatus (JGA) in each nephron, causing single nephron glomerular filtration rate (SNGFR) to be inversely dependent on the tubular flow to the macula densa. However, the long-term significance of TGF, especially in the chronic regulation of renal hemodynamics, sodium and water balance and blood pressure remains to be determined. We found that macula densa expresses �?±, �?², and �?³ splice variants of neuronal NO synthase (NOS1) and the expressions of NOS1�?² were significantly higher than that of NOS1�?±. To study the physiological significance of the NOS1�?² in the macula densa, we bred NKCC2 Cre mice with NOS1 floxed mice to produce macula densa specific NOS1 knockout (MD-NOS1KO) mice. The TGF response was significantly enhanced in MD-NOS1KO mice. GFR, urine flow and Na+ excretion were significantly lower in the MD-NOS1KO than in control mice following acute volume expansion. Mean arterial pressure (MAP) significantly increased in MD-NOS1KO mice fed a high salt diet or in response to infusion of Ang II plus a high salt diet. The results indicate that NOS1�?² is a primary isoform of NOS1 expressed in the macula densa and that deletion of NOS1�?² from the macula densa enhances TGF response, blunts the natriuretic response to acute volume expansion and promotes the development of salt-sensitive hypertension. These findings provide a novel mechanism for salt sensitivity of blood pressure and demonstrate the significance of TGF response in long-term control of sodium excretion and blood pressure.

Biography

Email: ruisheng@health.usf.edu