L-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in rats

Abstract

We evaluated whether l-proline (Pro) supplementation improves redox status and nitric oxide (NO) bioavailability and prevents or delays angiotensin II (AngII)-induced hypertension.Male Sprague-Dawley rats were distributed to four experimental groups: Pro + AngII (Pro-Ang), Pro + Saline (Pro-Sal), Vehicle + AngII (Veh-Ang) and Veh + Saline (Veh-Sal). Pro solution (2 g.kg−1·day−1) or water (vehicle) were orally administered, from day 0 to day 21. AngII (200 ng.kg−1.min−1) or saline were infused (s.c.) from day 7 to day 21. Systolic blood pressure (SBP) was measured by the tail-cuff method. From day 20–21, animals were kept on metabolic cages for 24h-urine collection. On day 21, urine and blood were collected for further quantification of redox status biomarkers, NO-related markers (urinary nitrates and nitrites, U-NOx; plasma asymmetric dimethylarginine, P-ADMA), metabolic and renal parameters.Pro prevented the AngII-induced SBP rise [mean (95% CI), Day 19: Pro-AngII, 137 (131; 143) vs. Veh-AngII, 157 (151; 163) mm Hg, P < 0.001]. Pro-AngII rats also had increased values of U-NOx, systemic and urinary total antioxidant status (TAS), urinary H2O2 and plasma urea, as well as reduced P-ADMA and unaltered urinary isoprostanes. Plasma Pro was inversely correlated with P-ADMA (r = −0.52, p = 0.0009) and positively correlated with urinary TAS (r = 0.55, p = 0.0005) which, in turn, was inversely correlated with P-ADMA (r = −0.56, p = 0.0004). Furthermore, urinary H2O2 values decreased across P-ADMA tertiles (p for linear trend = 0.023).These results suggest that Pro reduces P-ADMA levels and improves redox status, thereby increasing NO bioavailability and counteracting the AngII-induced SBP rise. H2O2 and TAS modulation by Pro may contribute to the reduced P-ADMA concentration.