Direct Vasodilators

1

What is a direct smooth muscle arterial vasodilator?

Direct arterial vasodilators are blood pressure–lowering medications characterized by a decrease in peripheral resistance mediated by relaxation of smooth muscle in arterioles. Two medications commonly recognized in this class include hydralazine and minoxidil.

2

What is the mechanism of action of direct arterial vasodilators?

Hydralazine acts on the arterial vessels, causing vasodilation and reduction of vascular resistance and blood pressure. The intracellular mechanisms mediating smooth muscle relaxation are not completely understood, but recent ex vivo studies suggest that the primary action is inhibition of inositol triphosphate (IP3) induced release of calcium from the sarcoplasmic reticulum.

Minoxidil produces smooth muscle relaxation by opening energy-dependent adenosine triphosphate (ATP) potassium channels, allowing potassium efflux to cause smooth muscle relaxation.

Direct vasodilators have minimal effect on nonvascular smooth muscle and the venous circulation or any direct effect on cardiomyocyte function.

3

What are the hemodynamic changes associated with direct vasodilators?

The reduction in afterload associated with direct vasodilators results in activation of the sympathetic nervous system with an increase in heart rate, cardiac contractility, stroke volume, and cardiac output ( Fig. 33.1 ). Hydralazine can decrease peripheral resistance by up to 75%, but the resultant hypotensive effect is offset by an increase in cardiac output of 50% to 75%. This counterproductive compensatory effect can be mitigated by coadministration of beta-blockers and diuretics.