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(Hypertension. 2008;51:791.)
© 2008 American Heart Association, Inc.

Original Articles

Nitric Oxide Synthase Inhibition Promotes Endothelium-Dependent Vasodilatation and the Antihypertensive Effect of L-Serine

Ramesh C. Mishra; Saswati Tripathy; Kaushik M. Desai; Dale Quest; Yanjie Lu; Jawed Akhtar; Venkat Gopalakrishnan

From the Department of Pharmacology (R.C.M., S.T., K.M.D., Y.L., V.G.), Division of Cardiology, Royal University Hospital (J.A.), College of Medicine, and the College of Nursing (D.Q.), University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

Correspondence to Dr Venkat Gopalakrishnan, professor and head, Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E5 Canada. E-mail venkat.gopal{at}usask.ca

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 N^G-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 µmol/L) vasodilatation in endothelium-intact but not in endothelium-denuded vessels. It was abolished by the inclusion of a combination of apamin (SK_Ca channel inhibitor) and TRAM-34 (IK_Ca channel inhibitor) or ouabain (Na⁺ pump inhibitor) and Ba²⁺ (K_ir 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 K_Ca channels present on the endothelium.

Key Words: amino acids • blood pressure • endothelium • hypertension • vasodilation

Related Article:

Blood Pressure Reduction, Potassium Channels, and the Endothelium: Insights From L-Serine

Jorge E. Jalil
Hypertension 2008 51: 626-628. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				J. E. Jalil Blood Pressure Reduction, Potassium Channels, and the Endothelium: Insights From L-Serine Hypertension, March 1, 2008; 51(3): 626 - 628. [Full Text] [PDF]