title: Endothelin-1 vasoconstrictor tone increases with age in healthy men but can be reduced by regular aerobic exercise.
abstract: 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 ( approximately 65%) in the older versus younger men. In response to BQ-123, resting forearm blood flow increased ( approximately 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.
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, 354 UCB, Boulder, CO 80309, USA.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Van Guilder
authors.forename: Christian M
authors.initials: CM
authors.lastname: Westby
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Greiner
authors.forename: Brian L
authors.initials: BL
authors.lastname: Stauffer
authors.forename: Christopher A
authors.initials: CA
authors.lastname: DeSouza
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000502:physiology; D000704:Analysis of Variance; D001823:Body Composition; D015331:Cohort Studies; D003326:Coronary Circulation / Q000502:physiology; D003327:Coronary Disease / Q000209:etiology / Q000517:prevention & control*; D019332:Endothelin-1 / Q000097:blood / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology*; D015444:Exercise / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000502:physiology; D011336:Probability; D011379:Prognosis; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D019332:Endothelin-1