R. Mishra, S. Tripathy, K. Desai
Mar 1, 2008
Citations
2
Influential Citations
29
Citations
Journal
Hypertension
Abstract
l-serine is a precursor of central neurotransmitters. Its cardiovascular effects are largely unstudied. We compared the in vitro effects of l-serine and acetylcholine in phenylephrine-constricted third-order branches of mesenteric arterioles in the NO synthase inhibitor NG-nitro l-arginine methyl ester (l-NAME), pretreated hypertensive rats, and a control group of normotensive male Sprague-Dawley rats. The changes in mean arterial pressure and heart rate evoked by acute intravenous infusion of either l-serine (0.1 to 3.0 mmol/kg) or acetylcholine (0.1 to 10.0 nmol/kg) were determined in anesthetized rats. l-serine evoked concentration-dependent (10 to 200 &mgr;mol/L) vasodilatation in endothelium-intact but not in endothelium-denuded vessels. It was abolished by the inclusion of a combination of apamin (SKCa channel inhibitor) and TRAM-34 (IKCa channel inhibitor) or ouabain (Na+ pump inhibitor) and Ba2+ (Kir channel inhibitor) or when the vessels were constricted by potassium chloride. The maximal response to l-serine was higher in the l-NAME treatment group (control 20% versus l-NAME 40%) in relation to the maximal response to acetylcholine (control 93% versus l-NAME 79%). l-serine evoked a rapid, reversible, dose-dependent fall in mean arterial pressure without increasing heart rate and was more pronounced in l-NAME–treated rats (maximal response: >60 mm Hg) than in the control rats (maximal response: 25 mm Hg). This was inhibited (P<0.01) by apamin+charybdotoxin pretreatment. The in vitro and in vivo data confirm that l-serine promotes vasodilatation in resistance arterioles and evokes a greater fall in mean arterial pressure in NO synthase–inhibited hypertensive rats via activation of apamin and charybdotoxin/TRAM-34-sensitive KCa channels present on the endothelium.