L-arginine is a nutritionally dispensable amino acid, which is involved in many physiologic processes including nitric oxide (NO) synthesis. The L-arginine/NO pathway is a part of the normal process of cardiovascular autoregulation and it is probably deficient in patients with essential hypertension. L-arginine supplement prevent the induction of hypertension in rat-sensitive models and produce hypotension in healthy humans when given intravenously. The benefit of L-arginine supplementation has not clearly been demonstrated in humans with essential hypertension. This study will explore the in vivo adaptation mechanisms involved in arginine metabolism and homeostasis and in whole body nitric oxide production (measured as NO excretion) in such patients. We will also correlate metabolic data with a complete and exhaustive clinical evaluation. Ten patients will receive a controlled diet with a normal L-arginine intake (56.1 mg/Kg/day) and then an arginine-supplemented (561 mg/Kg/day) isonitrogenous diet. Clinical outcome measures include daily blood pressure, as well as catecholamines, hANP, AVP, aldosterone, cGMP level and renin activity on day one and day seven of each diet period. At the end of each diet period, an 8h stable-isotopic labelled tracer study will be performed to evaluate the arginine, ornithine and urea fluxes as well s the NO production via measurement of nitrite/nitrate. This project will shed new light on the potential benefit of arginine supplement in diseases involving the L-arginine/NO pathway, such as essential hypertension. It will also define more completely the metabolic basis underlying body arginine homeostasis in human adults.
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