The Sympathetic Nervous System Is Involved in the Maintenance but Not Initiation of the Hypertension Induced by N ω -Nitro- l -Arginine Methyl Ester

Abstract

Abstract Studies in anesthetized animals have advanced the theory that there is an important neurogenic component to the hypertension caused by pharmacological inhibition of nitric oxide, but studies in conscious animals have produced conflicting evidence for and against this theory. To try to reconcile the seemingly contradictory data, we hypothesized that the neurogenic component of this hypertension is time dependent such that the sympathetic nervous system is involved primarily in the maintenance, rather than the initiation, of the hypertension. We measured intra-arterial pressure in conscious, unrestrained rats with and without guanethidine-induced sympathectomy during varying durations of intravenous N ω -nitro- l -arginine methyl ester (L-NAME). The major new finding is that sympathectomy had no effect on the hypertensive response to bolus injections of L-NAME but in the same rats it produced a greater than 50% attenuation in the hypertension seen after 6 days of continuous L-NAME (change in mean arterial pressure, 23±4 versus 55±4 mm Hg, P <.01, sympathectomy versus control). Using 8-hour infusions of L-NAME, we found that 60 minutes was the minimum time required for detecting a sympathectomy-sensitive component of L-NAME–induced hypertension. Furthermore, we demonstrate that the magnitude of this component increases further between 8 hours to 6 days of continuous L-NAME: it accounted for only 18% of the total hypertensive response at 8 hours but 61% after 6 days. From these experiments, we conclude that the importance of the sympathetic system in the pathogenesis of L-NAME–induced hypertension accrues slowly over hours and days, and thus its importance can be overlooked by focusing on the initial phase of the hypertension.