Endothelin-A-mediated vasoconstriction during exercise with advancing age.

The endothelin-1 vasoconstrictor pathway contributes to age-related elevations in resting peripheral vascular tone primarily through activation of the endothelin subtype A (ET(A)) receptor. However, the regulatory influence of ET(A)-mediated vasoconstriction during exercise in the elderly is unknown. Thus, in 17 healthy volunteers (n = 8 young, 24±2 years; n = 9 old, 70±2 years), we examined leg blood flow, mean arterial pressure, leg arterial-venous oxygen (O2) difference, and leg O2 consumption (VO2) at rest and during knee-extensor exercise before and after intra-arterial administration of the ET(A) antagonist BQ-123. During exercise, BQ-123 administration increased leg blood flow to a greater degree in the old (+29±5 mL/min/W) compared with the young (+16±3 mL/min/W). The increase in leg blood flow with BQ-123 was accompanied by an increase in leg VO2 in both groups, suggesting a reduced efficiency following ET(A) receptor blockade. Together, these findings have identified an age-related increase in ET(A)-mediated vasoconstrictor activity that persists during exercise, suggesting an important role of this pathway in the regulation of exercising skeletal muscle blood flow and maintenance of arterial blood pressure in the elderly.