Relaxin (RLX) lowers plasma levels of asymmetric dimethylarginine (ADMA) during chronic angiotensin II (ANGII) infusion

Abstract

The endogenous nitric oxide (NO) synthase inhibitor ADMA is increased during chronic ANGII infusion. We and others have shown that RLX attenuates hypertension and increases NO bioavailability. Therefore, this study tested the hypothesis that RLX reduces ADMA levels in ANGII hypertension. Male Sprague‐Dawley rats were given ANGII (400ng/kg/min) or vehicle (CON) for 6 weeks via minipump. RLX was then administered (4 μg/h) to half of the rats for the last 4 weeks (n=6–9 per 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 both ANGII and CON). ANGII also increased plasma ADMA levels vs CON (1.1±0.2 vs 0.23±0.02 μmol/L, p<0.05), and ADMA levels were normalized by RLX (0.29±0.02 μmol/L, p<0.05 vs ANGII). To determine the mechanisms responsible for the decrease in plasma ADMA, we investigated expression of protein arginine methyl transferase (PRMT) and the expression and activity of dimethylarginine dimethylaminohydrolase (DDAH). PRMT1 abundance was increased in the lung with ANGII vs CON (1.0±0.2 vs 1.5±0.2 units, p<0.05), but was not reduced by RLX (1.7±0.7 units). No changes in PRMT3 in the lung or PRMT1 in the kidney cortex or liver were observed. Furthermore, no changes in DDAH expression or activity were observed in the kidney cortex or liver. Our data do not reflect actions of relaxin in the kidney cortex, liver, or lung to reduce ADMA levels. Relaxin may have effects on other target organs such as by modulating DDAH activity in the vasculature.