Guanosine-5’-monophosphate, oxidation

Cyclic Guanosine Monophosphate Guanylyl Cyclase Nitric Oxide Carbon Monoxide... 

Dipyridamole exerts its effect by inhibition of platelet phosphodiesterase E5, increasing cyclic guanosine monophosphate and cyclic adenosine monophosphate (cAMP). By inhibiting its uptake and metabolism by erythrocytes, dipyridamole also increases the availability of adenosine within blood vessels, promoting inhibition of platelet aggregation and local vasodilatation. " Dipyridamole may also inhibit cAMP phosphodiesterase in platelets, which further increases cAMP levels and may enhance endothelial nitric oxide production, contributing to its antithrombotic effect. Existing trials of dipyridamole in stroke have focused on secondary prevention and will be discussed briefly. 

Fig. 3. Mechanisms of vasocontraction and vasorelaxation in endothelial and smooth muscle cells. COX cyclooxygenase, eNOS endothelial nitric oxide synthase, HO-1 heme oxygenase-1, EET epoxyeicosatrienoic acid, EDHF endothelium-derived hyperpolariz-ing factor, PGI2 prostaglandin I2, NO nitric oxide, CO carbon monoxide, PLC phospholipase C, IP3 inositol 1,4,5-trisphosphate, DAG diacylglycerol, ER/SR endo-plasmic/sarcoplasmic reticulum, AC adenylyl cyclase, cAMP cyclic adenosine monophosphate, sGC soluble guanylyl cyclase, cGMP cyclic guanosine monophosphate.

Fig. 1. The EDRF/NO pathway in vascular smooth muscle. Vasodilatation by nitrates at a cellular level. Nitrates, nitrites, and nitroprusside-Na are able to release nitric oxide (NO), which stimulates the conversion of GTP into cyclic guanosine monophosphate (cGMP), thus causing vasodilatation. The release of EDRF (=NO) from endothelial cells can be stimulated by various endogenous compounds. Endogenous EDRF (=NO) then causes vasodilatation, similar to the NO released by...

Garg, U. C., and Hassid, A. (1989). Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J. Clin. Invest. 83, 1774-1777. 

Erection occurs when adrenergic-induced sinusoid tone is antagonized by sacral parasympathetic stimulation that produces sinusoidal relaxation primarily by synthesis and release of the nonadrenergic-noncholinergic (NANC) neurotransmitter nitric oxide (NO). The contribution of acetylcholine-dependent release of NO from the vascular endothelium is uncertain. In vitro electrical stimulation of isolated corpus cavemosum strips (with or without endothelium) produces sinusoidal relaxation by release of neurotransmitters within nerve terminals that is resistant to adrenergic and cholinergic blockers. Inhibitors of the synthesis of NO or of guanosine monophosphate (GMP),... 

Sildenafil increases the release of nitric oxide and increases the levels of cyclic guanosine monophosphate (cGMP), a smooth muscle relaxant. Sildenafil enhances the effects of nitric oxide by inhibiting phosphodiesterase 5, an enzyme found primarily in the penis that degrades cGMP. As a result, increased levels of cGMP in the corpus cavemosum enhance smooth muscle relaxation, the inflow of blood, and erection. Sildenafil has no effect in the absence of sexual stimulation (see Figure 60.1). 

---