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

Abstract

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.

Impact of presymptomatic COVID-19 on vascular and skeletal muscle function: a case study

“…COVID-19 is associated with increased sympathetic activity which results in peripheral vasoconstriction. We, and others, have consistently reported that age-and disease-related increases in sympathetic activity are associated with diminished blood flow, especially at lower exercise intensities (44)(45)(46). As exercise intensity increases, local factors overcome this sympathetically-mediated vasoconstriction, a process termed functional sympatholysis (47), potentially resulting in preserved blood flow at higher exercise intensities, even with COVID-19.…”

Sympathetic nervous system activation and heart failure: Current state of evidence and the pathophysiology in the light of novel biomarkers

“…Furthermore, a subsequent study showed that muscle SNA was significantly higher while peak oxygen uptake was significantly lower in patients with ischemic vs nonischemic cardiomyopathy[ 171 ]. The most recent clinical study also demonstrated that the α-adrenergic-mediated vasoconstriction in HFrEF patients elicited a marked decrease in exercising skeletal muscle blood flow thus contributing to reduced exercise capacity in this population[ 172 ]. Finally, HF patients present with a high degree of chronotropic incompetence and attenuated heart rate response to exercise which is partially due to postsynaptic desensitization of the β-adrenergic receptor pathways[ 173 ].…”

Cardiac and Vascular α1-Adrenoceptors in Congestive Heart Failure: A Systematic Review

“…Multiple studies have shown an increase in vascular responsiveness to α 1 -AR stimulation in animals [114][115][116][117]119,120,122,[129][130][131]. On the contrary, others have reported desensitization of α 1 -ARs in the peripheral vasculature in animals [102,121,[132][133][134][135][136] and in humans [137][138][139][140], while numerous studies failed to demonstrate any alterations of the α 1 -AR responsiveness in vessels from animals [105,123,133,[141][142][143] and humans [144]. Inconsistency in findings might originate from differences in the anatomy and function of distinct vascular beds.…”