The L-arginine-nitric oxide pathway plays a crucial role in endothelial vasodilation, with nitric oxide acting as the endothelium-derived relaxing factor.
Biochemistry of the L-arginine-NO pathway The endothelium plays a crucial role in the vasodila- tor response to a large variety of drugs. In 1980 Furchgott and co-workers had discovered that the pres- ence of an intact endothelium is mandatory for the relaxation of isolated blood vessels by acetylcholine in vitro, whereas acetylcholine induced contractions in arterial preparations in which the endothelium had been injured or mechanically removed l. It was soon discovered that endothelial cells release an unknown soluble relaxing factor, which was named endothelium derived relaxing factor 2, and which in 1987 was shown to be virtually identical with nitric oxide (NO) 3, in response to a variety of pharmacological and physiological stimuli (Fig. 1). Subsequently the amino acid L-arginine was iden- tified as the biological precursor of NO 4. NO acti- vates vascular smooth muscle soluble guanylate cyclase, increasing cyclic GMP and decreasing intracellular Ca2+ concentrations, among other effects 5. Cyclic GMP as the second messenger mediates many of the biological effects of NO, among which are-in the cardiovascular system-relaxation of smooth muscle and inhibition of platelet aggregation 5. The enzyme converting L-arginine to NO was purified and cloned in 1991 6,7, and was named nitric oxide synthase (NOS).
Böger et al. (1996) conducted a review in Atherosclerosis. L-arginine-nitric oxide pathway was evaluated. The L-arginine-nitric oxide pathway plays a crucial role in endothelial vasodilation, with nitric oxide acting as the endothelium-derived relaxing factor.