Nitric oxide formation and plasma L-arginine levels in pulmonary hypertensive rats.

The elevation of plasma L-arginine levels stimulates nitric oxide (NO) synthesis, but the underlying mechanisms are not yet understood. We examined the role of physiological changes in pulmonary arteries on endogenous NO production. Male Wistar rats were divided into following groups: (1) control rats receiving normal water orally, (2) ARG rats receiving L-arginine water orally, (3) MCT rats injected with monocrotaline (MCT) on day 0 and receiving normal water orally, and (4) MCT+ARG rats injected with MCT on day 0 and receiving L-arginine water orally. The rats were studied after 23 days of dietary intervention. In MCT+ARG rats, supplemental L-arginine exhibited a significant pulmonary vasodilatory effect, as shown by a decreased pulmonary arterial pressure (PAP) (P<0.001), decreased right ventricular hypertrophy (P<0.01), and improved endothelium-dependent relaxation (P<0.01). Also L-arginine inhibited the elevation of plasma endothelin-1 (P<0.01). Oral L-arginine administration increased plasma L-arginine levels about twofold, but in only MCT+ARG rats (i.e., not in ARG rats) did the urinary nitrate excretion significantly increase (P<0.05), which is an indicator of endogenous NO formation. Oral administration of L-arginine is effective against pulmonary vascular remodeling. The data also suggest that the initial elevation of PAP is important for the induction of endogenous NO synthesis.