Thromboxane A 2 receptors contribute to the exaggerated exercise pressor reflex in male rats with heart failure

• Published in: Physiological reports Vol. 9; no. 18; p. e15052
• Main Authors: Butenas, Alec L E, Rollins, Korynne S, Williams, Auni C, Parr, Shannon K, Hammond, Stephen T, Ade, Carl J, Hageman, K Sue, Musch, Timothy I, Copp, Steven W
• Format: Journal Article
• Language: English
• Published: United States 01.09.2021
• Subjects: Animals; Blood Pressure; Heart Failure - metabolism; Heart Failure - physiopathology; Male; Motor Activity; Muscle Contraction; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiology; Nerve Endings - metabolism; Nerve Endings - physiology; Rats; Rats, Sprague-Dawley; Receptors, Thromboxane A2, Prostaglandin H2 - metabolism; Reflex; Sensory Receptor Cells - metabolism; Sensory Receptor Cells - physiology; mechanoreflex; blood pressure; cyclooxygenase; sensory neurons; muscle afferents
• ISSN: 2051-817X
• DOI: 10.14814/phy2.15052

Mechanical and metabolic signals associated with skeletal muscle contraction stimulate the sensory endings of thin fiber muscle afferents and produce reflex increases in sympathetic nerve activity and blood pressure during exercise (i.e., the exercise pressor reflex; EPR). The EPR is exaggerated in patients and animals with heart failure with reduced ejection fraction (HF-rEF) and its activation contributes to reduced exercise capacity within this patient population. Accumulating evidence suggests that the exaggerated EPR in HF-rEF is partially attributable to a sensitization of mechanically activated channels produced by thromboxane A receptors (TxA -Rs) on those sensory endings; however, this has not been investigated. Accordingly, the purpose of this investigation was to determine the role played by TxA -Rs on the sensory endings of thin fiber muscle afferents in the exaggerated EPR in rats with HF-rEF induced by coronary artery ligation. In decerebrate, unanesthetized rats, we found that injection of the TxA -R antagonist daltroban (80 μg) into the arterial supply of the hindlimb reduced the pressor response to 30 s of electrically induced 1 Hz dynamic hindlimb muscle contraction in HF-rEF (n = 8, peak ∆MAP pre: 22 ± 3; post: 14 ± 2 mmHg; p = 0.01) but not sham (n = 10, peak ∆MAP pre: 13 ± 3; post: 11 ± 2 mmHg; p = 0.68) rats. In a separate group of HF-rEF rats (n = 4), we found that the systemic (intravenous) injection of daltroban had no effect on the EPR (peak ΔMAP pre: 26 ± 7; post: 25 ± 7 mmHg; p = 0.50). Our data suggest that TxA -Rs on thin fiber muscle afferents contribute to the exaggerated EPR evoked in response to dynamic muscle contraction in HF-rEF.