Endothelin-1, aging and hypertension

Abstract

Purpose of review: Endothelin-1 system activation plays an important role in the etiology of atherosclerotic vascular disease. Aging and hypertension are two independent cardiovascular risk factors that have been shown to exhibit increased endothelin-1 system activation. This review focuses on the cardiovascular effects of the endothelin system, its relation to aging and hypertension, as well as potential treatment options.

Recent findings: Many of the cardiovascular complications associated with both aging and hypertension are attributable, in part, to endothelial dysfunction, particularly vasomotor dysregulation. To date most studies have focused on the effects of aging and hypertension on endothelium-dependent nitric oxide-mediated vasodilation. However, endothelin-1-mediated vasoconstrictor tone increases with age and contributes to the pathogenesis of hypertension. Pharmacologic approaches to reduce endothelin-1 system activation have produced limited results and are largely disease-specific. In contrast, regular aerobic exercise has been shown to be extremely effective at reducing endothelin-1 system activity.

Summary: Both aging and hypertension represent important cardiovascular disease risk factors that are characterized by increased endothelin-1-mediated vasoconstrictor tone. Future studies are needed to elucidate pharmacologic options for reducing endothelin-1 system activity especially in older hypertensive adults, though regular aerobic exercise must continue to be a point of emphasis for maintaining/improving vascular health.

Figure 1. Forearm blood flow responses to selective ET_A receptor blockade with BQ123 in (a) young (26 ± 1 year) and older (62 ± 2 years) men and (b) normotensive (47 ± 1 yr) and hypertensive (51 ± 2 yr) adults

Vasodilator response in both the older and hypertensive adults is indicative of increased endothelin-1-mediated vasoconstrictor tone [(b) adapted from [16]]. Values are mean ± SEM.