ABSTRACT
NEW FINDINGS: What is the central question of this study? How do locomotor muscle metabo- and mechanoreceptor expression compare in heart failure patients and controls? Do relationships exist between the protein expression and cardiopulmonary responses during exercise with locomotor muscle neural afferent feedback inhibition? What is the main finding and its importance? Heart failure patients exhibited greater protein expression of transient receptor potential vanilloid type 1 and cyclooxygenase-2 than controls. These findings are important as they identify receptors that may underlie the augmented locomotor muscle neural afferent feedback in heart failure. ABSTRACT: Heart failure patients with reduced ejection fraction (HFrEF) exhibit abnormal locomotor group III/IV afferent feedback during exercise; however, the underlying mechanisms are unclear. Therefore, the purpose of this study was to determine (1) metabo- and mechanoreceptor expression in HFrEF and controls and (2) relationships between receptor expression and changes in cardiopulmonary responses with afferent inhibition. Ten controls and six HFrEF performed 5 min of cycling exercise at 65% peak workload with lumbar intrathecal fentanyl (FENT) or placebo (PLA). Arterial blood pressure and catecholamines were measured via radial artery catheter. A vastus lateralis muscle biopsy was performed to quantify cyclooxygenase-2 (COX-2), purinergic 2X3 (P2X3 ), transient receptor potential vanilloid type 1 (TRPV 1), acid-sensing ion channel 3 (ASIC3 ), Piezo 1 and Piezo 2 protein expression. TRPV 1 and COX-2 protein expression was greater in HFrEF than controls (both P < 0.04), while P2X3 , ASIC3 , and Piezo 1 and 2 were not different between groups (all P > 0.16). In all participants, COX-2 protein expression was related to the percentage change in ventilation (r = -0.66) and mean arterial pressure (MAP) (r = -0.82) (both P < 0.01) with FENT (relative to PLA) during exercise. In controls, TRPV 1 protein expression was related to the percentage change in systolic blood pressure (r = -0.77, P = 0.02) and MAP (r = -0.72, P = 0.03) with FENT (relative to PLA) during exercise. TRPV 1 and COX-2 protein levels are elevated in HFrEF compared to controls. These findings suggest that the elevated TRPV 1 and COX-2 expression may contribute to the exaggerated locomotor muscle afferent feedback during cycling exercise in HFrEF.
Subject(s)
Afferent Pathways , Exercise , Heart Failure/physiopathology , Mechanoreceptors/metabolism , Quadriceps Muscle/physiology , Acid Sensing Ion Channels , Aged , Case-Control Studies , Cyclooxygenase 2 , Female , Fentanyl/administration & dosage , Humans , Ion Channels , Male , Middle Aged , Receptors, Purinergic P2X3 , TRPV Cation ChannelsABSTRACT
In this review, we highlight the underlying mechanisms responsible for the sex differences in the exercise pressor reflex (EPR), and, importantly, the impact of sex hormones and menopausal status. The EPR is attenuated in premenopausal women compared with age-matched men. Specifically, activation of the metaboreflex (a component of the EPR) results in attenuated increases in blood pressure and sympathetic vasomotor outflow compared with age-matched men. In addition, premenopausal women exhibit less transduction of sympathetic outflow to the peripheral vasculature than men. In stark contrast, postmenopausal women exhibit an augmented EPR arising from exaggerated metaboreflex-induced autonomic and cardiovascular reflexes. We propose that metaboreflex-induced autonomic and cardiovascular changes associated with menopause majorly contribute to the elevated blood pressure response during dynamic exercise in postmenopausal women. In addition, we discuss the potential mechanisms by which sex hormones in premenopausal women may impact the EPR as well as metaboreflex.
