Chronic Stress Deteriorated Nitric Oxide Production in Wistar Rats Exposed to a Low Dose of L-NAME

The aim of this study was to investigate the effect of chronic crowding stress in condition of disturbed nitric oxide (NO) production by a low dose of NO synthase inhibitor NGNitro-L-arginine methyl ester (L-NAME). Male, 12 weeks old, Wistar rats were exposed to crowding stress (200 cm2 per rat, 5 rats per cage), L-NAME treatment (1.5 mg/kg/day in drinking water) or their combination for 8 weeks. Control and L-NAME treated rats were kept 4 rats per cage (480 cm2 per rat). Blood pressure (BP) was determined by tail-cuff method. Nitric oxide synthase activity was determined by conversion of [3H]-L-arginine to [3H]-L-citrulline. Vascular function was investigated using Mulvany’s myograph in isometric conditions. Stress and L-NAME alone failed to affect BP at the end of experiment. However, combined L-NAME + stress exposure resulted in significant elevation of BP and left ventricular (LV) hypertrophy. Chronic stress failed to affect NOS activity in the hypothalamus, hypophysis, LV and aorta. Low-dose L-NAME-treatment paradoxically significantly elevated NO synthase activity in the aorta and LV, had no effect in the hypothalamus and reduced NO production in the hypophysis. Combined L-NAME + stress exposure reduced NO production in all tissues investigated. Acetylcholine-induced relaxation of the femoral artery was elevated in stressed and L-NAME-treated rats but significantly reduced in the L-NAME + stress group. Results suggest that chronic stress can markedly deteriorate NO production and vascular function in conditions when NO production is disturbed by a low dose of L-NAME in normotensive rats. Abbreviations: NG-nitro-L-arginine methyl ester (L-NAME); blood pressure (BP); left ventricle (LV); nitric oxide (NO); cardiovascular system (CVS); hypothalamic-hypophyseal-adrenal axis (HHA); body mass (BM)