Long-term low dose L-NAME treatment in normotensive and borderline hypertensive rats

Abstract

This study investigated the effect of long-term low dose NG-nitro-L-arginine methyl ester (L-NAME) treatment in Wistar and borderline hypertensive rats (BHR). Male, 12 weeks old, BHR (offspring of SHR dams and Wistar sires) and Wistar rats were exposed to low dose L-NAME treatment (1.5 mg/kg/day) for 8 weeks. Blood pressure (BP) of Wistar and BHR before experiment (determined by tail-cuff) was (Mean±SEM) 111±3 (n=10), 136±2 (n=10) mm Hg (p<0.001). L-NAME elevated BP on weeks 3 and 6 in both W and BHR. After this period, BP decreased in both groups investigated. At the end of the experiment no differences in BP were observed in W (vs. control) while BP of BHR rats was still significantly elevated. Relative left ventricular weight was elevated in L-NAME-treated BHR vs. control. NO synthase activity (determined by conversion of [3H]arginine) in the aorta and left ventricle of Wistar rats was paradoxically elevated after the low dose L-NAME treatment (p<0.04 vs. control), an effect not observed in BHR. Acetylcholine-induced relaxation of the femoral artery of control Wistar rats was lower than that of BHR (57±3% vs. 68±4%, p<0.001). Low dose of L-NAME improved acetylcholine-induced relaxation in Wistar rats but had no effect in BHR. In conclusion, chronic low dose of L-NAME treatment led to development of hypertension only in BHR although their NO production and vasorelaxation were not altered. On the other hand, low dose of L-NAME elevated NO production and improved vascular relaxation in normotensive rats. The study was supported by VEGA 2/4156/26 and APVT-51-018004.