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Am J Physiol Regul Integr Comp Physiol. 2019 May 1;316(5):R512-R524. doi: 10.1152/ajpregu.00345.2018. Epub 2019 Feb 21.

α-Adrenergic receptor regulation of skeletal muscle blood flow during exercise in heart failure patients with reduced ejection fraction.

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Department of Exercise and Sport Science, University of Utah , Salt Lake City, Utah.
Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center , Salt Lake City, Utah.
Department of Internal Medicine, University of Utah , Salt Lake City, Utah.
Department of Nutrition and Integrative Physiology, University of Utah , Salt Lake City, Utah.
Department of Kinesiology and Applied Physiology, University of Delaware , Newark, Delaware.
Department of Anesthesiology, University of Utah , Salt Lake City, Utah.


Patients suffering from heart failure with reduced ejection fraction (HFrEF) experience impaired limb blood flow during exercise, which may be due to a disease-related increase in α-adrenergic receptor vasoconstriction. Thus, in eight patients with HFrEF (63 ± 4 yr) and eight well-matched controls (63 ± 2 yr), we examined changes in leg blood flow (Doppler ultrasound) during intra-arterial infusion of phenylephrine (PE; an α1-adrenergic receptor agonist) and phentolamine (Phen; a nonspecific α-adrenergic receptor antagonist) at rest and during dynamic single-leg knee-extensor exercise (0, 5, and 10 W). At rest, the PE-induced reduction in blood flow was significantly attenuated in patients with HFrEF (-15 ± 7%) compared with controls (-36 ± 5%). During exercise, the controls exhibited a blunted reduction in blood flow induced by PE (-12 ± 4, -10 ± 4, and -9 ± 2% at 0, 5, and 10 W, respectively) compared with rest, while the PE-induced change in blood flow was unchanged compared with rest in the HFrEF group (-8 ± 5, -10 ± 3, and -14 ± 3%, respectively). Phen administration increased leg blood flow to a greater extent in the HFrEF group at rest (+178 ± 34% vs. +114 ± 28%, HFrEF vs. control) and during exercise (36 ± 6, 37 ± 7, and 39 ± 6% vs. 13 ± 3, 14 ± 1, and 8 ± 3% at 0, 5, and 10 W, respectively, in HFrEF vs. control). Together, these findings imply that a HFrEF-related increase in α-adrenergic vasoconstriction restrains exercising skeletal muscle blood flow, potentially contributing to diminished exercise capacity in this population.


blood flow; exercise; heart failure; neurohumoral; sympathetic

[Available on 2020-05-01]

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