Nitric oxide elevate cGMP

Nitric oxide is synthesized from the amino acid arginine in a reaction catalysed by NOS I-arginine + 02 + NADPH — citrulline + NADP+ + NO (thiol, tetrahydrobiopterin, FMN and FAD being requisite cofactors in this process). NO subsequently acts by activating soluble GC, thereby successively causing elevation of cGMP and PKG activation. NO can also act by activating Ca2 1 -dependent K+ channels. 

Nitric oxide and NOS can be constitutive or inducible. Constitutive nNOS and eNOS occur in neuronal and endothelial cells, respectively, and are activated by CaM. In endothelial cells acetylcholine, bradykinin or blood flow derived shear stress elevate cytosolic Ca2+ with the successive consequences of eNOS activation by CaM, NO production, GC activation by NO, elevation of cGMP, PKG activation, specific protein phosphorylation, vascular smooth muscle relaxation and vascular dilation. 

Vasodilators have a number of different mechanisms of action. Some are smooth muscle relaxants that act directly on the blood vessels, e.g. glyceryl trinitate, hydralazine, isosorbide dinitrate, pentaerythritol tetranitrate, sodium nitroprusside and other nitrite and nitrate drugs, which are thought to mimic the actions of the endogenous mediator nitric oxide, which relaxes smooth muscle through elevation of cGMP (see nitrergic stimulants). 

NO), which activates cGMP-dependent protein kinase through stimulation of guanylyl cyclase and elevation of cGMP, relaxes arteries. Nitric oxide has also been reported to activate K channels directly in aortic smooth muscle (Bolotina et al., 1994), as well as activate K jp channels in rabbit mesenteric arteries (Murphy and Brayden, 1995). 

It has also been shown that atrial natriuretic factor (ANP), nitric oxide, and isosorbide dinitrite, which dilate arteries and increase intracellular cGMP levels, activate K tp channels suggesting the possibility that either elevation of cGMP or stimulation of cGMP-dependent protein kinase could activate K jp channels in smooth muscle (e.g., see Murphy and Bray den,... 

The inhibition of platelet activation is a critical component in the treatment and prevention of cardiovascular diseases and cerebral ischemia/thrombotic disorders. Nitric oxide and prostacyclins inhibit platelet activation by elevating intracellular levels of both cGMP and cAMP, respectively. In platelets, the most abundant PDE is PDE3A, which lowers the intracellular concentration of cAMP. Inhibitors of PDE3A serve as potential antiplatelet agents by elevating cAMP levels. One PDE3-type selective inhibitor cilostazol, which has both antiplatelet, antithrombotic, and vasodilatory effects, is used for the treatment of intermittent claudication and for the prevention of short- and medium-term vessel closure (22). 

---