Relaxin increases renal inner medullary NOS1‐β expression during chronic angiotensin II infusion

Abstract

Relaxin (RLX) attenuates hypertension and increases nitric oxide (NO) bioavailability. Because NO inhibits sodium reabsorption in the inner medullary collecting duct, this study tested the hypothesis that RLX increases expression of NO synthase (NOS) isoforms in the inner medulla during angiotensin II (ANGII) hypertension. Male Sprague‐Dawley rats were given ANGII (400ng/kg/min) or vehicle (CON) for 6 weeks via minipump. RLX was administered (4 μg/h) to half of the rats for the last 4 weeks (n=6–8/group). ANGII increased blood pressure vs CON (165±5 vs 104±3 mm Hg, p<0.05), and this was reduced by RLX (135±13, p<0.05 vs ANGII and CON). NO bioavailability, assessed by urinary nitrate/nitrite excretion, was reduced during ANGII hypertension (0.8±0.2 vs 2.5±0.2 μmol/day, p<0.05) but restored by RLX treatment (1.8±0.4 μmol/day). NOS3 protein expression and phosphorylation on serine 1177 were comparable in all groups. While no changes were observed in expression of NOS1‐α among groups, NOS1‐β expression was reduced in the renal inner medulla of rats with ANGII hypertension (0.5±0.1 vs 1.0±0.3 RDU, p<0.05) but restored with relaxin treatment (0.8±0.2 RDU, p<0.05 vs ANG). We suggest RLX increases NOS1‐β in the inner medulla to promote NO‐dependent inhibition of sodium reabsorption in the collecting duct, thereby contributing to the lower blood pressure observed following RLX treatment during ANG II infusion.