Role of {alpha}1-adrenergic vasoconstriction in the regulation of skeletal muscle blood flow with advancing age

Abstract

alpha(1)-Adrenergic vasoconstriction during dynamic leg exercise is diminished in younger individuals, although the extent of this exercise-induced "sympatholysis" in the elderly remains uncertain. Thus, in nine young (25 +/- 1 yr) and six older (72 +/- 2 yr) healthy volunteers, we evaluated changes in leg blood flow (ultrasound Doppler) during blood flow-adjusted intra-arterial infusion of phenylephrine (PE; a selective alpha(1)-adrenergic agonist) at rest and during knee-extensor leg exercise at 20, 40, and 60% of maximal work rate (WR(max)). To probe the potential contributors to exercise-induced changes in alpha(1)-adrenergic receptor sensitivity, exercising leg O(2) consumption (Vo(2)) and lactate efflux were also evaluated (n = 10). At rest, the PE-induced vasoconstriction (i.e., decrease in leg blood flow) was diminished in older (-37 +/- 3%) compared with young (-54 +/- 4%) subjects. During exercise, the magnitude of alpha(1)-adrenergic vasoconstriction in the active leg decreased in both groups. However, compared with young, older subjects maintained a greater vasoconstrictor response to PE at 40% WR(max) (-14 +/- 3%, older; -7 +/- 2%, young) and 60% WR(max) (-11 +/- 3%, older; -4 +/- 3%, young). It is possible that this observation may be attributed to lower absolute work rates in the older group, because, for a similar absolute work rate ( approximately 10 W) and leg Vo(2) ( approximately 0.36 l/min), vasoconstriction to PE was not different between groups (-14 +/- 3%; older; -17 +/- 5%, young). Together, these data challenge the concept of reduced sympatholysis in the elderly, suggesting instead that the inhibition of alpha(1)-adrenergic vasoconstriction in the exercising leg is associated with work performed and, therefore, more closely related to the rate of oxidative metabolism than to age per se.

Fig. 1.

Experimental timeline. Arrows indicate time intervals for leg blood flow measurements. PRE, preinfusion; PE, phenylephrine; KE, knee-extensor exercise; WR_max, maximal KE work rate.

Fig. 2.

PE-induced changes in resting and exercising leg blood flow (A), leg vascular conductance (B), and the difference in PE-induced vasoconstriction between rest and exercise, representing the “magnitude of sympatholysis” (C) in young (solid bars) and older (open bars) subjects. When these hemodynamic responses are viewed in terms of relative work rate (as a percentage of maximal effort), blunting of α₁-adrenergic vasoconstriction appears reduced in the elderly. *Significantly different than young, P < 0.05.

Fig. 3.

PE-induced changes in conduit vessel (common femoral artery) diameter at rest and during three levels of KE exercise in young (solid bars) and older (open bars) subjects. Younger subjects exhibited a marked constriction at rest, which was significantly attenuated during KE exercise. In contrast, only small changes in vessel diameter were seen in response to PE at rest and during exercise in older subjects. *Significantly different than young, P < 0.05. ¥Significantly different than rest, P < 0.05.

Fig. 4.

PE-induced changes in leg blood flow during three levels of KE exercise. When responses to PE are viewed either in terms of absolute work rate (top) or leg O₂ consumption (V̇o₂; bottom), a significant correlation may be seen, with similar slopes and y-intercept values between young and older groups. From this perspective, blunting of α₁-adrenergic vasoconstriction appears to depend partially on absolute work rate rather than age per se. m, Slope of linear regression; c, y-intercept of linear regression.