The participations of oxidative stress and vascular alpha adrenoceptor responsiveness in hypertension generated by Co-administration of high salt diet and subpressor dose of L-NNA (N-G-Nitro-L-Arginin) in rats

Co-administration of subpressor doses of N -nitro-L-arginine (L-NNA) and high salt diet (8 %) leads to hypertension. The roles of sympathetic nervous system, vascular alpha-adrenergic receptor responsiveness and oxidative stress in this model of hypertension is unclear. To verify whether salt dependence in this model is related to the extent of nitric oxide inhibition, vascular adrenoceptor responsiveness and increased oxidative stress, we administrated to adult male Sprague-Dawley rats a standard salt, or high salt diet and oral L-NNA treatment at either 5 or 25 mg/kg per day. Blood pressure was measured by using tail-cuff method, plasma NOx levels were measured by spectrophotometrically, urine and serum electrolytes, urine creatinin and protein by autoanalyser, urine 8-isoprostane and Prostacyclin (PGI2) by ELISA, and urine vanillylmandelic acid (VMA), homovanillic acid (HVA) and 5-Hydroxyindoleacetic acid (5-HIAA) by High Performance Liquid Chromatography (HPLC) method. Alpha-adrenergic receptor responses in isolated thorasic aorta rings were evaluated in ?in vitro? conditions. Low-dose L-NNA treatment induced a blood pressure augmentation only when associated with sodium overload. In rats receiving high-dose L-NNA, hypertension was aggravated by sodium excess. At 14th days of treatment, the urine VMA levels was significantly increased in rats receiving low-dose L-NNA with high salt diet compared with others. Also, vascular alpha-1 adrenergic receptor sensitivity in this group was significantly decreased. Administration of L-NNA or high salt diet did induce any changes in urine 8-isoprostane levels, whereas co-administration of L-NNA with high salt diet induced important changes. These findings indicate that the sympathetic nervous system activation and partly oxidative stress may participate in the development of hypertension induced by co-administration of high salt diet with subpressor dose of L-NNA in rats.