A 43-year-old man is being evaluated for occasional retrosternal chest pressure that develops with moderate exertion and sometimes occurs when resting. He does not use alcohol, tobacco, or illicit drugs. The patient has an extensive family history of coronary artery disease. His temperature is 36.7 C (98 F), blood pressure is 124/72 mm Hg, pulse is 81/min, and respirations are 14/min. Physical examination shows no abnormalities. Coronary angiography shows mild luminal irregularities but no significant obstructive lesions. Acetylcholine infusion during the procedure results in dilation of epicardial coronary vessels. A reaction involving which of the following amino acids is most likely responsible for the observed dilation?
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The vascular endothelium plays an important role in vasodilation mediated by acetylcholine, bradykinin, serotonin, substance P, and shear forces. These stimuli activate specific membrane receptors present on endothelial cells, leading to an increase in cytosolic calcium levels. This causes activation of endothelial nitric oxide synthase (eNOS), which synthesizes nitric oxide from arginine, NADPH, and O2. Nitric oxide then diffuses into the adjacent smooth muscle cells, where it activates guanylyl cyclase and increases formation of cyclic GMP. High levels of cyclic GMP activate protein kinase G, which causes a reduction in cytosolic calcium levels and relaxation of vascular smooth muscle cells.
The availability of arginine for synthesizing nitric oxide depends on several factors, including exogenous food intake, endogenous synthesis, intracellular storage and degradation, and the presence of asymmetrical dimethylarginine (an endogenous analog of arginine that works as a competitive inhibitor of eNOS).
Educational objective:
Nitric oxide is synthesized from arginine by nitric oxide synthase. As a precursor of nitric oxide, arginine supplementation may play an adjunct role in the treatment of conditions that improve with vasodilation, such as stable angina.