Abstract Title:

Acute administration of l-arginine restores nitric oxide-mediated relaxation in isolated pulmonary arteries from pulmonary hypertensive exercise trained rats.

Abstract Source:

Eur J Pharmacol. 2008 Feb 26;581(1-2):148-56. Epub 2007 Nov 28. PMID: 18164288

Abstract Author(s):

Lucie Goret, Stéphane Tanguy, Isabelle Guiraud, Michel Dauzat, Philippe Obert

Article Affiliation:

JE2426, Laboratory Physiology of Cardiovascular Adaptations to Exercise, Faculty of Sciences, Avignon University, France. lucie.goret@univ-montp1.fr

Abstract:

Hypoxia-induced pulmonary hypertension is associated with an impairment of nitric oxide-mediated vasorelaxation in the pulmonary circulation that is not prevented by exercise training. The present study was designed to test the hypothesis that a decrease in l-arginine bioavailability could be involved in this blunted response to exercise training. Male Wistar rats were randomly assigned to 4 groups: normotensive sedentary, normotensive trained, pulmonary hypertensive sedentary, pulmonary hypertensive trained. Pulmonary hypertension was induced by chronic exposure to hypobaric hypoxia (PIO(2) approximately 90 mmHg). Endothelium-dependent vasorelaxation to acetylcholine (10(-8)-10(-4) M) with or without l-arginine (10(-3) M) and/or nitro-l-arginine methyl ester (5.10(-6) M) was assessed on isolated pulmonary arterial rings. Maximal relaxation to acetylcholine was impaired in both pulmonary hypertensive groups. Acute l-arginine supplementation improved acetylcholine-induced vasorelaxation in the pulmonary hypertensive trained rats (P<0.01), to the level obtained in the normotensive sedentary ones, but not in the pulmonary hypertensive sedentary rats. This improvement was abolished when nitro-l-arginine methyl ester was added to the organ bath and was accounted for by an increase in eNOS protein content. These results confirm that the potential beneficial effect of exercise on nitric oxide-mediated pulmonary artery vasorelaxation is partly blunted by deleterious effects of hypoxia on l-arginine bioavailability. Further studies are needed to evaluate the benefit of the combination of exercise training and l-arginine supplementation for the treatment of pulmonary hypertension.

Study Type : Animal Study

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