Number 28, 2005
Sex and the Heart

Glossary

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Gary D. Lopaschuk

Nitric oxide activates guanylyl cyclase
Guanylyl cyclase is the enzyme responsible for converting guanylyl triphosphate to cyclic guanosine monophosphate (cGMP). One of the prominent effects of cGMP is smooth muscle relaxation. Release of nitric oxide by endothelial cells is a potent vasodilator. The actions of nitric oxide are now known to be due to a stimulation of guanylyl cyclase, that results in an increase in cGMP levels and smooth muscle relaxation.

Cyclic guanosine monophosphate
Cyclic guanylate monophosphate (cGMP) is produced from guanylate triphosphate (GTP) via the enzyme guanylyl cyclase. cGMP has numerous actions as an intracellular signalling molecule, including relaxation of smooth muscle. The vasodilatory effect of nitric oxide on smooth muscle is mediated by the production of cGMP by guanylyl cyclase.

Phosphodiesterase type-5 (PDE-5) inhibitors
PDE-5 is the enzyme that metabolises cyclic guanosine monophosphate (cGMP). Therefore, PDE-5 inhibitors will prevent the degradation of cGMP and increase tissue levels of cGMP. A well known example of a PDE-5 inhibitor is sildenafil (marketed as Viagra^®). In addition to its smooth muscle relaxing effects in the penis, sildenafil can also induce pulmonary and coronary vasodilation, precondition the myocardium, reduce platelet activation, and potentially reduce early graft occlusion. As a result, PDE-5 inhibitors have potential in the treatment of both pulmonary hypertension and ischemic heart disease.