PMID: 6168849Sep 1, 1981Paper

Mechanism of the antihypertensive action of DL-alpha-monofluoromethyldopa: implications for the role of the sympathetic nervous system in maintenance of elevated blood pressure in spontaneously hypertensive rats

Journal of Cardiovascular Pharmacology
J R FozardJ Koch-Weser

Abstract

We investigated the mechanism of the antihypertensive action of DL-alpha-monofluoromethyldopa (MFMD), an irreversible inhibitor of L-aromatic amino acid decarboxylase, in spontaneously hypertensive rats (SHR). MFMD, 25 mg/kg i.p. daily for 3 days, reduced mean arterial blood pressure by 47 +/- 11 mm Hg (n = 6; p less than 0.001). The effect was associated with marked attenuation of the responses to stimulation of the whole sympathetic outflow in pithed preparations and with substantial reductions in the norepinephrine concentrations of hearts and portal veins. Similar functional and biochemical deficits were produced in age-matched, Wistar--Kyoto, normotensive rats, but blood pressure in these animals fell only by an average of 8 +/- 4 mm Hg (n = 5; NS). Blood pressure of SHR, lowered by MFMD, was restored to pretreatment levels by infusion with dopamine (0.1 mg/kg/min for 5 min), and there was a concomitant return towards normal of both the peripheral sympathetic transmitter stores and the response to stimulation of the nerves supplying the cardiovascular system. Neither the dopamine nor the norepinephrine concentrations of the brain, depleted by treatment with MFMD, were altered following infusion of dopamine. These results p...Continue Reading

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