Exaggerated sympathetic and cardiovascular responses to dynamic mechanoreflex activation in rats with heart failure: Role of endoperoxide 4 and thromboxane A2 receptors.

Abstract

The primary purpose of this investigation was to determine the role played by endoperoxide 4 receptors (EP4-R) and thromboxane A2 receptors (TxA2-R) during isolated dynamic muscle mechanoreflex activation in rats with heart failure with reduced ejection fraction (HF-rEF) and sham-operated healthy controls. We found that injection of the EP4-R antagonist L-161,982 (1μg) into the arterial supply of the hindlimb had no effect on the peak pressor response to dynamic hindlimb muscle stretch in HF-rEF (n=6, peak ∆MAP pre: 27±7; post: 27±4mmHg; P=0.99) or sham (n=6, peak ∆MAP pre: 15±3; post: 13±3mmHg; P=0.67) rats. In contrast, injection of the TxA2-R antagonist daltroban (80μg) into the arterial supply of the hindlimb reduced the pressor response to dynamic hindlimb muscle stretch in HF-rEF (n=11, peak ∆MAP pre: 28±4; post: 16±2mmHg; P=0.02) but not sham (n=8, peak ∆MAP pre: 17±3; post: 16±3; P=0.84) rats. Our data suggest that TxA2-Rs on thin fibre muscle afferents contribute to the exaggerated mechanoreflex in HF-rEF.