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

The objective of this study was to determine in conscious dogs the rol e of endothelium-derived nitric oxide in mediating the arterial pressu re 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) di d not change throughout the experiment in one group (n=4). In another group (n=6), 1 day after infusion of this inhibitor was started, sodiu m intake increased from 80 to 300 mmol/d during 4 consecutive days. In hibition of nitric oxide synthesis in dogs with normal sodium intake i nduced a significant decrease in natriuresis and diuresis (P<.05) with out changes in arterial pressure. However, in dogs treated with the ni tric 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 inta ke was elevated and remained increased the following 3 days. In a diff erent group of dogs (n=5), the increment of sodium intake during 4 day s did not induce changes in arterial pressure when nitric oxide synthe sis 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 o nly with the nitric oxide synthesis inhibitor (82+/-19 mmol sodium) or with high sodium intake (36+/-13 mmol sodium). Our results demonstrat ed that dogs fail to handle appropriately a prolonged increase in sodi um intake when nitric oxide synthesis is inhibited, and as a consequen ce, arterial pressure increases significantly. This elevation in arter ial pressure seems to be secondary, at least partly, to an increase in extracellular fluid volume. It is strongly suggested that hypertensio n is a necessary compensation for maintaining sodium balance when nitr ic oxide synthesis is chronically diminished.