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Chapter: Modern Pharmacology with Clinical Applications: Antihypertensive Drugs

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Vasodilators: Mechanism of Action

Available evidence suggests that a single unifying mech-anism does not exist but rather that various vasodilators may act at different places in the series of processes that couple excitation of vascular smooth muscle cells with contraction.

Mechanism of Action

Available evidence suggests that a single unifying mech-anism does not exist but rather that various vasodilators may act at different places in the series of processes that couple excitation of vascular smooth muscle cells with contraction. For example, the vasodilators known as cal-cium channel antagonists block or limit the entry of cal-cium through voltage-dependent channels in the mem-brane of vascular smooth muscle cells. In this way, the calcium channel blockers limit the amount of free intra-cellular calcium available to interact with smooth mus-cle contractile proteins .

 

Other vasodilators, such as diazoxide and minoxidil, cause dilation of blood vessels by activating potassium channels in vascular smooth muscle. An increase in potassium conductance results in hyperpolarization of the cell membrane, which will cause relaxation of vas-cular smooth muscle.

Another group of drugs, the so-called nitrovasodila-tors, of which nitroprusside is an example, activate solu-ble guanylate cyclase in vascular smooth muscle, which brings about an increase in the intracellular levels of cyclic guanosine monophosphate (cGMP). Increases in cGMP are associated with vascular smooth muscle re-laxation. The action of the nitrovasodilators appears to be quite similar to that of the endogenous vasodilator released by a variety of stimuli from endothelial cells of blood vessels. This substance, originally named en-dothelial-derived relaxing factor, or EDRF, is nitric ox-ide or a closely related nitrosothiol compound. The knowledge that the nitrovasodilators generate nitric ox-ide in vivo suggests that this substance may be the final common mediator of a number of vascular smooth mus-cle relaxants.

 

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