Role of L-arginine in nitric oxide production in health and hypertension.

1. l-Arginine is the substrate for vascular nitric oxide (NO) formation. Under normal physiological conditions, intracellular l-arginine levels far exceed the K(m) of NO synthase for l-arginine. However, endogenous NO formation is dependent on extracellular l-arginine concentrations, giving rise to the concept of the 'l-arginine paradox'. 2. Nitric oxide production in epithelial and endothelial cells is closely coupled to cellular l-arginine uptake, indicating that l-arginine transport mechanisms play a major role in the regulation of NO-dependent function. 3. Consistent with the data in endothelial and epithelial cells are functional data indicating that exogenous l-arginine can increase renal vascular and tubular NO bioavailability and thereby influence kidney perfusion, function and arterial pressure. The integrated effect of increased cellular l-arginine transport is to lower arterial pressure. Therefore, the use of l-arginine in the treatment of hypertension warrants investigation. 4. Low NO bioavailability is central to the development and maintenance of hypertension and to related endothelial dysfunction and target organ damage. We propose that l-arginine can interrupt the vicious cycle that initiates and maintains low NO in hypertension by increasing the formation of NO.