SALT-INDUCED INCREASE IN ARTERIAL-PRESSURE DURING NITRIC-OXIDE SYNTHESIS INHIBITION

The objective of this study was to determine in conscious dogs the role of endothelium-derived nitric oxide in mediating the arterial pressure and renal response to a prolonged increment of sodium intake. After a control period of 3 days, an inhibitor of nitric oxide synthesis, N(G)-nitro-L-arginine-methyl ester, was infused intravenously during 5 consecutive days (0.1 mug/kg per minute). Sodium intake (80 mmol/d) did not change throughout the experiment in one group (n=4). In another group (n=6), 1 day after infusion of this inhibitor was started, sodium intake increased from 80 to 300 mmol/d during 4 consecutive days. Inhibition of nitric oxide synthesis in dogs with normal sodium intake induced a significant decrease in natriuresis and diuresis (P<.05) without changes in arterial pressure. However, in dogs treated with the nitric oxide synthesis inhibitor, mean arterial pressure increased from 95.2+/-3.3 to 106.2+/-4.0 mm Hg (P<.01) the first day that sodium intake was elevated and remained increased the following 3 days. In a different group of dogs (n=5), the increment of sodium intake during 4 days did not induce changes in arterial pressure when nitric oxide synthesis was not inhibited. Cumulative sodium balance was higher (P<.01) in dogs treated simultaneously with the nitric oxide synthesis inhibitor and high sodium intake (158+/-21 mmol sodium) than in those treated only with the nitric oxide synthesis inhibitor (82+/-19 mmol sodium) or with high sodium intake (36+/-13 mmol sodium). Our results demonstrated that dogs fail to handle appropriately a prolonged increase in sodium intake when nitric oxide synthesis is inhibited, and as a consequence, arterial pressure increases significantly. This elevation in arterial pressure seems to be secondary, at least partly, to an increase in extracellular fluid volume. It is strongly suggested that hypertension is a necessary compensation for maintaining sodium balance when nitric oxide synthesis is chronically diminished.