Blood Pressure Reduction, Potassium Channels, and the Endothelium

Abstract

In this issue of Hypertension , Mishra et al1 compared the in vitro effects of the amino acid l-serine, a precursor of central neurotransmitters, and acetylcholine in phenylephrine-constricted mesenteric arterioles in N G-nitro-l-arginine methyl ester (l-NAME)-pretreated hypertensive rats, as well as in normotensive rats.1 l-Serine evoked concentration-dependent vasodilatation in endothelium-intact but not in endothelium-denuded vessels. This response to l-serine was abolished by a combination of apamin (a small conductance Ca2+-activated K+ channel inhibitor) and TRAM-34 (an intermediate conductance Ca2+-activated K+ channel inhibitor), ouabain (Na+ pump inhibitor) and barium chloride (an inward-rectifier K+ channel inhibitor), or when the vessels were constricted by potassium chloride. In addition, the authors determined in vivo changes in mean arterial blood pressure and heart rate induced by acute intravenous infusion of either l-serine or acetylcholine in anesthetized rats. The maximal response to l-serine was higher in the l-NAME treatment group in contrast to the maximal response to acetylcholine. l-Serine evoked a rapid, reversible, dose-dependent fall in mean arterial pressure without increasing heart rate, which was more pronounced in l-NAME-treated hypertensive rats than in the control rats. This acute hypotensive effect of l-serine was significantly inhibited by apamin and charybdotoxin pretreatment, a combination that blocks Ca-activated K channels or endothelium-derived hyperpolarizing factor (EDHF). The authors discussed that the acute dose-dependent response to l-serine may be because of activation of vascular/endothelial KCa channels (exaggerated when the NO system is blunted in the chronic l-NAME-pretreated …