Effects of L-dopa and inhibitors of decarboxylase and monoamine oxidase on brain noradrenaline levels and blood pressure in spontaneously hypertensive rats.

Abstract

Abstract Acute administration of l-dopa (200 mg/kg) resulted in a significant decrease in blood pressure of the spontaneously hypertensive (SH) rat. Simultaneous treatment with a peripheral decarboxylase inhibitor (3,4-dihydroxyphenyl-2-hydrazino-2-methylpropionic acid; MK 485) potentiated this effect while treatment with a decarboxylase inhibitor that penetrates the central nervous system (4-bromo-3-hydroxybenzyloxyamine; NSD 1055) tended to block the effect of l-dopa. In general, only treatments that increased brainstem noradrenaline were effective in reducing blood pressure. In young SH rats chronic treatment with l-dopa and a peripheral decarboxylase inhibitor significantly retarded the development of hypertension over four weeks. Treatment of SH rats with 3 daily doses (100 mg/kg each) of p-chlorophenylalanine resulted in a complete loss of 5-hydroxy-tryptamine and a slight reduction of noradrenaline in the brainstem. The blood pressure of these animals was slightly increased over that of the control SH rats. Treatment of several groups of SH rats with a monoamine oxidase inhibitor (pargyline) in various combinations with l-dopa and a peripheral decarboxylase inhibitor resulted in a wide range of noradrenaline levels in the brainstem. There appeared to be a highly significant inverse correlation between brainstem noradrenaline and blood pressure. The findings are consistent with central noradrenergic modulation of blood pressure in the rat.