A specific inhibitor of nitric oxide formation from <scp>l</scp>‐arginine attenuates endothelium‐dependent relaxation

TLDR

The study used the specific inhibitor l‑NG‑monomethyl‑l‑arginine (l‑NMMA) to probe the role of l‑arginine in basal and stimulated nitric oxide production underlying endothelium‑dependent relaxation. l‑Arginine (10–100 µM) caused modest but significant endothelium‑dependent relaxations, whereas its inhibitor l‑NMMA (1–300 µM) produced small contractions and blocked relaxations induced by acetylcholine, calcium ionophore, substance P, or l‑arginine, effects that were reversed by l‑arginine but not d‑arginine, confirming l‑arginine as the physiological precursor of nitric oxide for endothelium‑dependent relaxation.

Abstract

The role of l ‐arginine in the basal and stimulated generation of nitric oxide (NO) for endothelium‐dependent relaxation was studied by use of N G ‐monomethyl l ‐arginine ( l ‐NMMA), a specific inhibitor of this pathway. l ‐Arginine (10–100 μ m ), but not d ‐arginine (100 μ m ), induced small but significant endothelium‐dependent relaxations of rings of rabbit aorta. In contrast, l ‐NMMA (1–300 μ m ) produced small, endothelium‐dependent contractions, while its enantiomer N G ‐monomethyl‐ d ‐arginine (d‐NMMA; 100 μ) had no effect. l ‐NMMA (1–300 μ m ) inhibited endothelium‐dependent relaxations induced by acetylcholine (ACh), the calcium ionophore A23187, substance P or l ‐arginine without affecting the endothelium‐independent relaxations induced by glyceryl trinitrate or sodium nitroprusside. The inhibition of endothelium‐dependent relaxation by l ‐NMMA (30 μ m ) was reversed by l ‐arginine (3–300 μ m ) but not by d ‐arginine (300 μ m ) or a number of close analogues (100 μ m ). The release of NO induced by ACh from perfused segments of rabbit aorta was also inhibited by l ‐NMMA (3–300 μ m ), but not by d ‐NMMA (100 μ m ) and this effect of l ‐NMMA was reversed by l ‐arginine (3–300 μ m ). These results support the proposal that l ‐arginine is the physiological precursor for the basal and stimulated generation of NO for endothelium‐dependent relaxation.