Endothelin-1 vasoconstrictor tone increases with age in healthy men but can be reduced by regular aerobic exercise

Increased endothelin-1-mediated vasoconstrictor tone has been linked to the etiology of a number of pathologies associated with human aging, including hypertension, congestive heart failure, and coronary artery disease. However, it is currently unclear whether aging, per se, is associated with enhanced endothelin-1 system activity. We hypothesized that endothelin-1 vasoconstrictor activity is greater in healthy older compared with young men and that regular aerobic exercise is an effective intervention for reducing endothelin-1 vasoconstrictor tone in older previously sedentary men. Forearm blood flow (plethysmography) responses to intra- arterial infusion of endothelin-1 (5 pmol/ min; for 20 minutes) and selective (BQ-123; 100 nmol/ min; for 60 minutes) and nonselective ( BQ-123+BQ-788; 100 nmol/min; for 60 minutes) endothelin- 1 receptor blockade were determined in 28 healthy, sedentary men: 13 younger (age: 27 +/- 1 years) and 15 older (age: 62 +/- 2 years). The vasoconstrictor response to endothelin-1 was significantly blunted (approximate to 65%) in the older versus younger men. In response to BQ-123, resting forearm blood flow increased (approximate to 20%; P<0.05) in the older but not in the younger men. The addition of BQ-788 to BQ-123 did not significantly affect the blood flow responses to BQ-123 in either group. Eight of the 15 older sedentary men completed a 3-month aerobic exercise intervention. After the intervention, the vasoconstrictor response to endothelin-1 was markedly increased ( 225%; P<0.05), whereas BQ-123 resulted in modest vasoconstriction in the previously sedentary older men. These results demonstrate that endothelin-1-mediated vasoconstrictor tone increases with age in healthy men but can be alleviated with regular aerobic exercise.