Temperature modulates P2X receptor-mediated cardiovascular responses to muscle afferent activation

Abstract

Static muscle contraction increases ATP release into the muscle interstitial space. Elevated ATP in muscle stimulates thin fiber muscle afferents and increases blood pressure via engagement of purinergic P2X receptors. In addition, ATP activates P2X receptors and enhances cardiovascular responses induced by stimulation of muscle mechanoreceptors. In this study, we examined whether elevated muscle temperature would attenuate and whether reduced temperature would potentiate P2X effects on reflex muscle responses. alpha,beta-Methylene ATP (alpha,beta-MeATP) was injected into the arterial blood supply of hindlimb muscle to stimulate P2X receptors, and muscle stretch was induced to activate mechanically sensitive muscle afferents as alpha,beta-MeATP was injected in 10 anesthetized cats. Femoral arterial injection of alpha,beta-MeATP (1.0 mM) increased mean arterial pressure (MAP) by 35+/-5 (35 degrees C), 26+/-3 (37 degrees C), and 19+/-3 mmHg (39 degrees C; P<0.05 vs. 35 degrees C), respectively. Muscle stretch (2 kg) elevated MAP. The MAP response was significantly enhanced 34% and 36% when alpha,beta-MeATP (0.2 mM) was arterially infused 5 min before muscle stretch at 35 degrees and 37 degrees C, respectively. However, as muscle temperature reached 39 degrees C, the stretch-evoked response was augmented only 6% by alpha,beta-MeATP injection, and the response was significantly attenuated compared with the response with muscle temperature of 35 degrees and 37 degrees C. In addition, we also examined effects of muscle temperature on alpha,beta-MeATP enhancement of the cardiovascular responses to static muscle contraction while the muscles were freely perfused and the circulation to the muscles was occluded. Because muscle temperature was 37 degrees C, arterial injections of alpha,beta-MeATP significantly augmented contraction-evoked MAP response by 49% (freely perfused) and 53% (ischemic condition), respectively. It is noted that this effect was significantly attenuated at a muscle temperature of 39 degrees C. These data indicate that the effect of P2X receptor on reflex muscle response is sensitive to alternations of muscle temperature and that elevated temperature attenuates the response.

Performance in the Heat—Physiological Factors of Importance for Hyperthermia‐Induced Fatigue

“…In case of the P2X receptor, it has been shown that decreases in temperature increases P2X activity (148). In other words, an increased muscle temperature will decrease P2X activity and this would suggest that higher muscle temperatures might attenuate muscle reflexes (94). In contrast, increases in temperature increase the TRPV1 receptor activity (313), which would suggest that hyperthermia will facilitate muscle reflex responses to a given metabolic response.…”

Purinergic Signaling and Blood Vessels in Health and Disease

“…a,b-MeATP evokes reflex cardiovascular responses in muscle microvessels, via P2X receptors, when injected into the arterial supply of the cat hindlimb vasculature (Li and Sinoway, 2002;Hanna et al, 2002;Gao et al, 2006). P2X receptors can produce vasoconstriction in exercising canine skeletal muscle (Buckwalter et al, 2003(Buckwalter et al, , 2004.…”

Exaggerated Pressor Response in Relation to Attenuated Muscle Temperature Response during Contraction in Ischemic Heart Failure

“…The effect of P2X receptor on reflex muscle response has recently been reported to be sensitive to alternations of T m (Gao et al, 2006). This prior study further suggests that elevated T m attenuates the pressor response to static muscle contraction.…”

“…Contractions induced by electrical stimulation of the sciatic nerve were then performed in nine healthy control rats and 10 MI rats. Static contraction of the triceps surae muscle was conducted at frequencies of 30 Hz (2.5 times motor threshold and 0.1 ms duration; Gao et al, 2006). Stimulation was sustained for 1 min.…”

“…Thus, it was necessary to study contraction-induced increase in T m in order to better understand heightened sympathetic activity in HF, likely due to P2X and TRPV1. Moreover, the published data have demonstrated that blood pressure response to stimulation of P2X receptors on muscle afferents is attenuated with increasing T m (Gao et al, 2006). This result suggests that higher T m blunts effects of P2X on the reflex pressor response.…”