Published online before print June 18, 2007, doi: 10.1161/HYPERTENSIONAHA.107.088294
(Hypertension. 2007;50:403.)
© 2007 American Heart Association, Inc.
Original Articles |
Endothelin-1 Vasoconstrictor Tone Increases With Age in Healthy Men But Can Be Reduced by Regular Aerobic Exercise
From the Integrative Vascular Biology Laboratory (G.P.V.D., C.M.W., J.J.G., B.L.S., C.A.D.), Department of Integrative Physiology, University of Colorado, Boulder; Department of Medicine (B.L.S., C.A.D.), University of Colorado at Denver Health Sciences Center, Denver; and Denver Health Medical Center (B.L.S.), Colo.
Correspondence to Christopher DeSouza, Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, 354 UCB, Boulder, CO 80309. E-mail desouzac{at}colorado.edu
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 (
65%) in the older versus younger men. In response to BQ-123, resting forearm blood flow increased (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.
Key Words: elderly • exercise • endothelin • blood flow regulation
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