Role of α₁-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.

Serum calcium revisited: associations with 24-h ambulatory blood pressure and cardiovascular reactivity in Africans

“…[33][34][35][36] This is supported by a human study, in which infusion of the a1-adrenergic receptor agonist, phenylephrine, in young (mean age: 25.1 years) and old (mean age: 72.2 years) subjects at rest caused a less pronounced vasoconstriction response in the leg arteries of the older subjects. 37 Therefore, a higher a1-adrenergic receptor density would render peripheral arteries more sensitive to serum calcium. Not surprisingly, calcium infusion in humans also raised systolic and diastolic blood pressure and total peripheral resistance in both hypertensive and normotensive subjects with no change in cardiac output, and infusion of the calcium channel blocker, verapamil, attenuated this increase in both total peripheral resistance and blood pressure.…”

Perfusion pressure and movement-induced hyperemia: evidence of limited vascular function and vasodilatory reserve with age

“…In agreement with these previous findings, the present investigation has documented that resting LBF and LVC in the old were ϳ30% and ϳ35% less than in the young, respectively, and this was independent of body posture. While reductions in LBF and LVC have been further evidenced during a variety of active exercise modalities (11,26,37,54,56), the complexity of physiological mechanisms associated with muscle contraction make it difficult to isolate the contribution of limb movement on limb hyperemia.…”

“…While LBF and LVC during exercise are also attenuated with age (11,26,37,56), due to the complexity of the physiological responses to exercise, the mechanisms responsible for age-related reductions in leg hyperemia are not fully understood.…”

Sex differences with aging in nutritive skeletal muscle blood flow: impact of exercise training, nitric oxide, and α-adrenergic-mediated mechanisms

“…Indeed, ␣-adrenergic blockade with phentolamine restores the attenuated leg blood flow in aged individuals, although a vasodilatory effect of similar magnitude was observed in the young (9). Despite enhanced MSNA in the aged, further sympathetic stimulation tends to have a reduced vasoconstrictor effect in aged compared with young individuals (53,67). Parker et al (53) observed reduced sympathetic vasoconstrictor activity upon a vasodilatory stimulus of the popliteal artery in aged vs. young women, while Wray et al (67) showed that aged men vasoconstrict less than young men upon ␣ 1 -agonism of the femoral artery.…”

“…Despite enhanced MSNA in the aged, further sympathetic stimulation tends to have a reduced vasoconstrictor effect in aged compared with young individuals (53,67). Parker et al (53) observed reduced sympathetic vasoconstrictor activity upon a vasodilatory stimulus of the popliteal artery in aged vs. young women, while Wray et al (67) showed that aged men vasoconstrict less than young men upon ␣ 1 -agonism of the femoral artery. No preexercise training age-associated alterations of ␣-adrenergic-mediated nutritive muscle blood flow were observed in the present study.…”