| Aging is an independent risk factor for the development of cardiovascular diseases, particularly atherosclerotic vascular disease. Many of the cardiovascular complications associated with aging (e.g., hypertension, arterial spasm, and myocardial infarction) are due, in part to endothelial dysfunction, specifically vasomotor dysregulation. In addition to the synthesis and release of relaxing factors, such as nitric oxide, the vascular endothelium also produces contracting factors, the most potent of which is endothelin (ET)-1. Increased ET-1 vasoconstrictor activity has been linked with hypertension, coronary artery disease, and congestive heart failure. However, little is known regarding the impact of vascular aging on ET-1- mediated vasoconstrictor activity in humans. Accordingly, the experimental aims of this dissertation were to determine if: (1) endogenous ET-1 vasoconstrictor activity increases with age in healthy, sedentary adult men and (2) a regular aerobic exercise training program can reduce the ET-1--mediated vasoconstrictor tone. To address these aims, an isolated forearm model was employed to assess: a) blood flow responses to exogenous ET-1 as well as the ET-A and ET-B receptor antagonists BQ-123 and BQ-788 before and after a 12-week home based aerobic exercise program. The results from these studies indicate that: (1) older men demonstrate increased ET-1 vasoconstrictor tone that is mediated predominantly by the ET-A receptor and (2) a relatively brief (3-month) period of habitual aerobic exercise training enhanced forearm vasoconstriction to exogenous ET-1. Taken together these studies demonstrate that the age-related increases in ET-1 production and vasoconstrictor tone may contribute to the increased cardiovascular risk and morbidity in older men. Furthermore, regular aerobic exercise training is an effective therapeutic strategy for improving endothelial function by reducing vasoconstrictor tone in older adults. |
