Impaired modulation of postjunctional α1 - but not α2 -adrenergic vasoconstriction in contracting forearm muscle of postmenopausal women.

KEY POINTS: Contraction-mediated blunting of postjunctional α-adrenergic vasoconstriction (functional sympatholysis) is attenuated in skeletal muscle of ageing males, brought on by altered postjunctional α1 - and α2 -adrenergic receptor sensitivity. The extent to which postjunctional α-adrenergic vasoconstriction occurs in the forearms at rest and during exercise in postmenopausal women remains unknown. The novel findings indicate that contraction-mediated blunting of α1 - (via intra-arterial infusion of phenylephrine) but not α2 -adrenergic (via intra-arterial infusion of dexmedetomidine) vasoconstriction was attenuated in postmenopausal women compared to young women. Additional important findings revealed that postjunctional α-adrenergic vasoconstrictor responsiveness at rest does not appear to be affected by age in women. Collectively, these results contribute to our understanding of local neurovascular control at rest and during exercise with age in women. ABSTRACT: Contraction-mediated blunting of postjunctional α-adrenergic vasoconstriction (functional sympatholysis) is attenuated in older males; however, direct confirmation of this effect remains unknown in postmenopausal women (PMW). The present study examined whether PMW exhibit augmented postjunctional α-adrenergic receptor vasoconstriction at rest and during forearm exercise compared to young women (YW). Eight YW (24 ± 1 years) and eight PMW (65 ± 1 years) completed a series of randomized experimental trials: (1) at rest, (2) under high flow (adenosine infusion) conditions and (3) during 6 min of forearm exercise at relative (20% of maximum) and absolute (7 kg) intensities. Phenylephrine (α1 -agonist) or dexmedetomidine (α2 -agonist) was administered during the last 3 min of each trial to elicit α-adrenergic vasoconstriction. Forearm vascular conductance (FVC) was calculated from blood flow and blood pressure. Vasoconstrictor responsiveness was identified as the change in FVC (%) during α-adrenergic agonist infusions from baseline (resting trial) or from steady-state conditions (high flow and exercise trials). During resting and high flow trials, the %FVC during α1 - and α2 -agonist stimulation was similar between YW and PMW. During exercise, α1 -mediated vasoconstriction was blunted in YW vs. PMW at relative (-6 ± 2% vs. -15 ± 3%) and absolute (-4 ± 2% vs. -14 ± 5%) workloads, such that blood flow and FVC were lower in PMW (P < 0.05 for all). Conversely, α2 -mediated vasoconstriction was similar between YW and PMW at relative (-22 ± 3% vs. -22 ± 4%; P > 0.05) and absolute (-19 ± 3% vs. -18 ± 4%; P > 0.05) workloads. Collectively, these findings demonstrate that despite similar α-adrenergic vasoconstrictor responsiveness at rest, PMW have a decreased ability to attenuate α1 -adrenergic vasoconstriction in contracting skeletal muscle.

Evidence of a greater functional sympatholysis in habitually aerobic trained postmenopausal women.

Habitual aerobic exercise attenuates elevated vasoconstriction during acute exercise (functional sympatholysis) in older men; however, this effect remains unknown in postmenopausal women (PMW). This study tested the hypothesis that PMW who participate in habitual aerobic exercise demonstrate a greater functional sympatholysis compared with their untrained counterparts. Nineteen PMW (untrained n = 9 vs. trained n = 10) performed 5 min of steady-state (SS) forearm exercise at relative [10% and 20% of maximum voluntary contraction (MVC)] and absolute (5 kg) contraction intensities. Lower-body negative pressure (LBNP) was used to increase sympathetic vasoconstriction during rest and forearm exercise. Brachial artery diameter and blood velocities (via Doppler ultrasound) determined forearm blood flow (FBF; ml/min). Forearm muscle oxygen consumption ([Formula: see text]; ml/min) and arteriovenous oxygen difference (a-vO2diff) were estimated during SS-exercise and SS-exercise with LBNP. Forearm vascular conductance (FVC; ml·min-1·100 mmHg-1) was calculated from FBF and mean arterial pressure (MAP; mmHg). Vasoconstrictor responsiveness was determined as the %change in FVC during LBNP. The reduction in FVC (% change FVC) during LBNP was lower in trained compared with untrained PMW at 10% MVC (-7.3 ± 1.2% vs. -13.0 ± 1.1%; P < 0.05), 20% MVC (-4.4 ± 0.8% vs. -8.6 ± 1.4%; P < 0.05), and 5 kg (-5.3 ± 0.8% vs. -8.9 ± 1.4%; P < 0.05) conditions, whereas there were no differences at rest (-32.7 ± 4.4% vs. -33.7 ± 4.0%). Peripheral (FVC, FBF, and [Formula: see text]) and the magnitude change in systemic hemodynamics (heart rate and MAP) did not differ between groups during exercise. Collectively, the findings present the first evidence suggesting that PMW who participate in aerobic exercise demonstrate a greater functional sympatholysis compared with untrained PMW during mild to moderate forearm exercise. NEW & NOTEWORTHY Habitual aerobic exercise attenuates the elevated sympathetic nervous system-induced vasoconstriction during an acute bout of exercise (improved functional sympatholysis) in aging men; however, this effect remains unknown in postmenopausal women (PMW). The novel findings of this study suggest that habitual aerobic exercise results in an enhanced functional sympatholysis in PMW. Conversely, habitual aerobic exercise does not alter blood flow and oxygen utilization during acute forearm exercise compared with PMW who do not habitually exercise.