A 50-year-old male is brought to the emergency room with chest pain and shortness of breath. He is given a medication that activates cGMP, resulting in relaxation of vascular smooth muscle. This medication is most likely a derivative of:
A. Creatine phosphate
B. S-Adenosyl Methionine
E. Nitric oxide
Answer- E- Nitric oxide
Nitric oxide is a highly reactive gas. It participates in many chemical reactions. Endothelium-derived relaxing factor was originally the name given to several proposed factors causing vasodilatation. The major endothelial derived relaxing factor was later discovered to be nitric oxide (NO).
Nitric oxide is synthesized by nitric oxide synthase (NOS) – Figure-1. There are three isoform of the NOS enzyme:
- Endothelial (eNOS),
- Neuronal (nNOS), and
- Inducible (iNOS) – each with separate functions.
Figure-1- Arginine is converted to Citrulline and nitric oxide in a reaction catalyzed by nitric oxide synthase. The enzyme requires NADPH and molecular oxygen for its action.
Once synthesized by eNOS it results in activation of guanylate cyclase to form cGMP, which in turn causes phosphorylation of several proteins through activation of c GMP dependent protein kinases that cause smooth muscle relaxation by decreasing the intracellular Ca++ concentration- Figure-2
Figure-2- Vasodilatation induced by nitric oxide
NO is an important regulator and mediator of numerous processes in the nervous, immune and cardiovascular systems, including smooth muscle relaxation.
Nitroglycerin, amyl nitrite, (isobutyl nitrite or similar) and other nitrite derivatives are used in the treatment of heart disease. The compounds are converted to nitric oxide, which in turn dilates the coronary artery, thereby increasing its blood supply. These drugs, however, are predominantly vasodilators; dilating peripheral veins and hence reducing venous return and preload to the heart. This reduces the oxygen requirement of the myocardium and subsequently lessens the anginal pain felt with myocardial ischemia.
As regards other options,
- Creatine phosphate is a high energy compound and is mainly synthesized in the brain, skeletal and heart muscle.
- S- Adenosyl Methionine is an important methyl group donor of the body and participates in the synthesis of various biologically important compounds.
- Glutathione is an important reducing agent.
- Melatonin is a derivative of Tryptophan, it participates in sleep wake cycle.
None of these compounds act by activating c GMP, thus the correct option is nitric oxide.
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