Endothelin-A-mediated vasoconstriction during exercise with advancing age

Abstract

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.

Keywords: Aging.; Arterial; Blood; Endothelin-1; Exercise; blood p; flow; ressure.

Figure 1.

Experimental protocol. Arrows indicate points at which leg blood flow was recorded and arterial and venous blood samples were obtained.

Figure 2.

Resting leg blood flow expressed as percent change (top) and absolute units (bottom) during continuous infusion of BQ-123 in the young (circles) and old (diamonds). ^‡Significant difference from young, p < .05; ^##significant difference from minute 0 in the old, p < .05.

Figure 3.

Leg blood flow (top) and BQ-123-induced changes in leg blood flow (bottom) during exercise in young (circles) and old (diamonds) participants. Data at the highest work rate (80% of maximum) represents the leg blood flow response in those participants whose maximal work rate was greater than 15W (n = 8, young; n = 5, old). *Significant difference from saline in both the young and the old, p < .05; **significant difference from saline in the old, p < .05; +significant difference from BQ-123-induced changes at rest in both the young and old, p < .05; ++significant difference from saline in the old, p < .05; ^‡significant difference from young, p < .05.

Figure 4.

Leg vascular conductance (top) and BQ-123-induced changes in leg vascular conductance (bottom) during exercise in young (circles) and old (diamonds) participants. Data at the highest work rate (80% of maximum) represents the leg blood flow response in those participants whose maximal work rate was greater than 15W (n = 8, young; n = 5, old). *Significant difference from saline in both the young and the old, p < .05; +significant difference from BQ-123-induced changes at rest in both the young and old, p < .05; ++significant difference from saline in the old, p < .05; ^‡significant difference from young, p < .05.

Figure 5.

Mean arterial pressure (top) and BQ-123-induced changes in mean arterial pressure (bottom) during exercise of relative intensity work rates in young (circles) and old (diamonds). *Significant difference from saline in both the young and the old, p < .05; +significant difference from BQ-123-induced changes at rest in both the young and old, p < .05; ^‡significant difference from young, p < .05.

Figure 6.

Leg blood flow and mean arterial pressure during multiple time points during the time control study in the young (black circles) and old (white circles) are displayed. No significant differences were observed between measurements at rest or at equivalent exercise intensities.