The mechanism of action of nitroglycerin and other organic nitrates is thought to involve an interaction with nitrate receptors that are present in vascular smooth muscle. Intact vascular endothelium is not necessary for the vasodilator action of the nitrates to be produced. The nitrate receptor possesses sulfhydryl groups, which reduce nitrate to inorganic nitrite and nitric oxide (NO). The formation of nitrosothiols, and possibly free NO, has been proposed to stimulate intracellular soluble guanylate cyclase, which leads to an increase in in-tracellular cyclic guanosine monophosphate (GMP) formation (Fig. 17.1). The increase in GMP results in vascular smooth muscle relaxation, possibly through inhibition of calcium entry via L-type calcium channels, decreased calcium release from the sarcoplasmic reticu-lum, or via an increase in calcium extrusion via a sar-colemmal Ca++-adenosine triphosphatase (ATPase).
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