Vasodilators

The drugs discussed in this section produce a direct relaxation of vascular smooth muscle and thereby their actions result in vasodilation. This effect is called direct because it does not depend on the innervation of vascular smooth muscle and is not mediated by receptors, such as adrenoceptors, cholinoreceptors, or receptors for histamine, that are acted on by classical transmitters and mediators.

The vasodilators decrease total peripheral resistance and thus correct the hemodynamic abnormality that is responsible for the elevated blood pressure in primary hypertension. In addition, because they act directly on vascular smooth muscle, the vasodilators are effective in lowering blood pressure, regardless of the etiology of the hypertension. Unlike many other antihypertensive agents, the vasodilators do not inhibit the activity of the sympathetic nervous system; therefore, orthostatic hypotension and impotence are not problems. Additionally, most vasodilators relax arterial smooth muscle to a greater extent than venous smooth muscle, thereby further minimizing postural hypotension.

Although vasodilators would appear to be ideal drugs for the treatment of hypertension, their effectiveness, particularly when they are used chronically, is severely limited by neuroendocrine and autonomic reflexes that tend to counteract the fall in blood pressure. How these reflexes compromise the fall in blood pressure produced by the vasodilators is shown in Fig. 20.1. The diagram does not show all of the possible interrelationships but rather is meant to draw attention to the most prominent reflex changes. These reflexes include an augmentation of sympathetic nervous activity that leads

Vasodilators t Sympathetic nervous activity

Relax vascular smooth muscle

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