Sodium sensitivity and sympathetic nervous system in hypertension induced by long-term nitric oxide blockade in rats

1. Pharmacological inhibition of nitric oxide (NO) synthesis is known to pr oduce acute and chronic hypertension in many animal species, but the underl ying mechanisms mediating the hypertension are not completely understood. I n particular, the pathogenetic roles of sodium sensitivity and the sympathe tic nervous system in this model of hypertension are controversial. The pre sent study was designed to test the hypothesis that longterm administration of the NO synthesis inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) t o male Sprague-Dawley rats would produce a sodium-sensitive hypertension an d that the enhanced activity of the sympathetic nervous system in this type of hypertension contributes to the sodium sensitivity. 2. N-G-Nitro-L-arginine methyl ester was added to drinking fluid for 8 week s at a concentration of 16 mg/dL, Rats received tap water for the first 4 w eeks of the study and were then divided into two groups and placed on eithe r a normal or high sodium intake (ingestion of either tap wafer or 0.9 % Na Cl, respectively). Awake systolic blood pressure was measured by the tail-c uff method every week, Urinary excretion rates of the stable NO metabolites and catecholamines during NO synthesis inhibition were examined. 3. Long-term administration of L-NAME produced a marked and sustained eleva tion in arterial pressure without altering urine flow, or sodium excretion rate. N-G-Nitro-L-arginine methyl ester-induced hypertension was accompanie d by a decreased urinary excretion of the stable NO metabolites NO2- and NO 3- and was aggravated when rats drank 0.9% NaCl in place of tap water. Urin ary excretion of adrenaline and noradrenaline, but not dopamine, in L-NAME- treated rats increased significantly within the first week of the study com pared with control rats. L-Arginine (2 g/dL in drinking fluid) completely r eversed the elevation of arterial pressure as well as the decrease in urina ry NO2- and NO3- excretion and the increased urinary excretion of catechola mines associated with L-NAME treatment by 3 weeks of concomitant administra tion. 4. These results suggest that long-term inhibition of NO synthesis produces a sodium-sensitive hypertension and that changes in sympathetic nerve acti vity may, at least in part, contribute to the sodium sensitivity in this ty pe of hypertension.