Mechanisms of decreased tubular flow-induced nitric oxide in Dahl salt-sensitive rat thick ascending limbs

Am J Physiol Renal Physiol. 2021 Jul 26. doi: 10.1152/ajprenal.00124.2021. Online ahead of print.ABSTRACTDahl salt-sensitive rat (SS) kidneys produce less nitric oxide (NO) than those of salt-resistant rats (SR). Thick ascending limb (THAL) NO synthase 3 (NOS3) is a major source of renal NO, and luminal flow enhances its activity. We hypothesized that flow-induced NO is reduced in SS THALs primarily due to NOS uncoupling and diminished NOS3 expression rather than scavenging. Rats were fed normal (NS) or high-salt (HS) diets. We measured flow-induced NO and superoxide in perfused THALs, and performed Western blots of renal outer medullas. For rats on NS, flow-induced NO was 35±6 arbitrary units (AU)/min in SR but only 11±2 AU/min in SS THALs (p<0.008). The superoxide scavenger tempol decreased the difference in flow-induced NO between strains by about 36% (p<0.020). The NOS inhibitor L-NAME decreased flow-induced superoxide 36 ± 8% in SS (p<0.02) but had no effect in SR THALs. NOS3 expression was not different between strains on NS. For rats on HS, the difference in flow-induced NO between strains was enhanced (SR: 44±10 vs SS: 9±2 AU/min; p<0.005). Tempol decreased the difference in flow-induced NO between strains by about 37% (p<0.012). L-NAME did not significantly reduce flow-induced superoxide in either strain. HS increased NOS3 expression in SR but not in SS THALs (p<0.003). We conclude: 1) on NS, flow-induced NO is diminished in SS THALs mainly due...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Source Type: research