Abstract

In 1967 Sattler and van Swieten established that the hypotensive action of clonidine was mediated by its central action. In 1995 we observed that nitric oxide (NO), acting centrally, had a physiologically important, tonic blood pressure-lowering action. In the current study, we determined whether the hypotensive action of clonidine, administered centrally, was mediated by its stimulation of the release of excess NO. Using the porphyrinic microsensor to determine NO concentrationin the nucleus tractus solitariusof brain slices from normotensive rats, we established that clonidine (50-150 nmol/L) caused a 5.6-fold increase in NO release. In the pentobarbital anesthetized rat, clonidine administered intracerebroventricularly (30 ng, ICV) caused an 8.5-fold increase in NO release. In the latter preparation, pretreatment of the rat with the nitric oxide synthase inhibitor L-NAME (2 micromol, ICV), 30 minutes before the clonidine, reduced its hypotensive effect from -21 mmHg to -3mmHg. We conclude that the antihypertensive action of clonidine is mediated by its stimulation of the release of NO in the blood pressure regulating centers of the brain.

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