Renal vascular L‐arginine metabolism, NO release and contraction in Angiotensin II hypertensive rats

Abstract

The effect of Angiotensin II (AngII) hypertension on L‐arginine metabolising enzymes and AngII induced vascular contraction and nitric oxide release was investigated because we found increased expressions in vessels from both kidneys of 2K1C rats and increased nitric oxide release from the non‐clipped kidney. Four groups of rats were infused with 80 ng/min AngII or saline for 14 days, and/or given 60 mg/kg/day Losartan. Gene expression was studied in isolated preglomerular vessels by RTPCR. Arteriolar contraction was studied using 10−10, 10−9, 10−8 and 10−7 mol/L of AngII and 10−4 mol/L L‐NAME in vessels isolated using the agar infusion/enzyme digestion method. Expressions of eNOS , caveolin‐1 and Arginase‐2 were not changed by AngII infusion. CAT‐1 (0.38±0.07 to 0.73±0.12, P<0.05), CAT‐2 (1.14±0.29 to 2.74±0.48), DDAH‐2 (1.09±0.27 to 2.3±0.46) and Arginase‐1 (1.08±0.17 to 1.82±0.22) were increased in AngII infused rats and normalised by Losartan. Losartan reduced the expression of eNOS (0.97±0.26 to 0.37±0.11 in controls; 0.8±0.16 to 0.36±0.1 in AngII infused rats) and caveolin‐1 (2.49±0.59 to 0.82±0.24 in controls and 2.59±0.61 to 1.1±0.25 in AngII infused rats). AngII induced contraction was enhaced in the AngII infused animals (47±15 % vs. 7±5 % at 10−10 mol/L AngII). Contraction at 10−10 mol/L AngII was enhaced by L‐NAME in AngII infused rats (96±4 %). In conclusion, Losartan affects eNOS and caveolin‐1 expression through an AT1 receptor independent pathway. CAT‐1, CAT‐2, DDAH‐2 and Arginase‐1 expressions in renal resistance vessels are regulated through the AT1 receptor, which may be of direct importance for nitric oxide synthesis and the regulation of renal blood flow as can be seen by the buffering effect of NO on the contraction of isolated arterioles in the vessels from AngII infused animals. The study was funded by Helsevest, Norway.