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

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(omega)-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.

Chemical sympathectomy alters regulation of body weight during prolonged ICV leptin infusion

“…A total of 15 injections were given 5 days a week, as originally described by Johnson and colleagues (27,29). This treatment protocol results in a permanent sympathectomy that has been verified by numerous investigators (27,29,35,(45)(46)(47), and we validated the functional integrity of postganglionic sympathetic nerve responses in representative adult animals from our treated group by measuring the increment in blood pressure after a 250 g/kg intravenous injection of tyramine. Arterial and venous catheters were inserted, and the rats had 5-7 days to recover before experiments were performed in conscious, unrestrained animals.…”

Rho/Rho-Kinase Pathway in the Brainstem Contributes to Hypertension Caused by Chronic Nitric Oxide Synthase Inhibition

“…There is evidence that L-NAME crosses the blood-brain barrier when administered orally 23 and the sympathetic nervous system is involved primarily in the maintenance, rather than initiation, of L-NAME-induced hypertension. 24,25 Furthermore, activation of the Rho/Rho-kinase pathway in the NTS plays an important role in the maintenance of the basal arterial blood pressure via the sympathetic nervous system. 17 In addition, activation of the pathway might be involved in the central nervous system mechanisms of hypertension in spontaneously hypertensive rats.…”

“…[3][4][5][6][7] The latency of the onset of the sympathectomy-sensitive component of intravenous infusion of L-NAME-induced hypertension, however, was 1 to 2 hours. 24 The latency of onset of neural component after oral administration of L-NAME might be longer than intravenous infusion; 24 hours is when the neural component of L-NAME-induced blood pressure elevation becomes apparent. Furthermore, the effect of intracisternal infusion of Y-27632 on SBP was expected to begin much faster than that of oral administration of L-NAME.…”

Redox Control of Renal Function and Hypertension

“…An extensive body of literature links the sympathetic nervous system (SNS) and hypertension (2,191,205,279,285). NO has been shown to play a central role in offsetting oxidative stress/SNS-mediated increase in arterial pressures (118).…”