Heat treatment improves the exaggerated exercise pressor reflex in rats with femoral artery occlusion via a reduction in the activity of the P2X receptor pathway

Abstract

Key pointsr During exercise, the blood pressure (BP) response is exaggerated in peripheral artery disease (PAD).r We examined whether heat treatment (HT) has beneficial effects on the exaggerated exercise pressor reflex in PAD rats.r With HT (increase in basal muscle temperature of ß1.5°C for 30 min, twice daily for three continuous days), the amplified BP response to muscle contraction is alleviated in PAD.r We demonstrated that HT attenuates the enhancement of the BP response induced by stimulation of P2X in muscle afferent nerves of PAD rats. HT also attenuates the upregulation of the P2X 3 and the increase in P2X currents in the muscle afferent neurons of PAD rats.r Previous heat exposure plays a beneficial role in modifying the exaggeration of the exercise pressor reflex in PAD and a reduction in the activity of the P2X receptor pathway is probably a part of the mechanism mediating this improvement.Abstract The current study was performed to examine if heat treatment (HT) has beneficial effects on the exaggerated exercise pressor reflex in rats with peripheral artery disease (PAD). We further determined if the temperature-sensitive P2X receptor is involved in the effects of HT. The pressor response to static muscle contraction and α,β-methylene ATP (αβ-me ATP, a P2X agonist) was examined. Western blot analysis was used to determine the protein levels of P2X 3 in the dorsal root ganglion (DRG), and the whole cell patch clamp was used to examine the amplitude of P2X currents in the DRG neurons. The basal muscle temperature (T m ) was lower in PAD rats than in control rats. T m was increased by ß1.5°C and this increase was maintained for 30 min. This HT protocol was performed tweice daily for three continuous days. A greater blood pressure (BP) response to contraction was observed in PAD rats. HT attenuated the amplification of the BP response in PAD rats. HT also attenuated the enhancement of the BP response induced by the arterial injection of αβ-me ATP in PAD rats. In addition, HT attenuated the upregulation of the Lu Qin received her PhD from The Chinese L. Qin and others J Physiol 598.8 P2X 3 and increased P2X currents in the DRG neurons of PAD rats. In conclusion, previous heat exposure plays an inhibitory role in modifying the exaggeration of the exercise pressor reflex in PAD and a reduction of the activity of the P2X receptor pathway is probably a part of mechanisms leading to the beneficial effects of HT.

One-Time Acute Heat Treatment Is Effective for Attenuation of the Exaggerated Exercise Pressor Reflex in Rats With Femoral Artery Occlusion

“…With the approach of ventral root stimulation in the current study, it was observed that the BP response to the skeletal muscle contraction was enhanced in PAD rats when compared with the control rats. This result was also consistent with what observed in the previous studies ( Liu et al, 2011 ; Qin et al, 2020 ). In addition, the exaggerated BP response was attenuated following increasing Tm by ~1.5°C ( Figure 2A ).…”

“…The elevated ATP concentration in the muscle interstitium enhances the expression and function of P2X 3 and the subsequent EPR response is exaggerated. Consistent with previous studies (Liu et al, 2011;Qin et al, 2020), the BP response following both muscle contraction and muscle stretch was higher in rats with femoral artery occlusion than that in control rats (Figures 2A,B). BP response to stimulation of P2X 3 by injection of αβ-me ATP, as a part of EPR activation, was also amplified in PAD rats (Figures 3A,B).…”

“…In our previous study (Qin et al, 2020), using a repeated heating exposure protocol, overexpression of P2X 3 protein in the DRG was attenuated in PAD rats following three-day heating treatment. As a consequence, the BP response to αβ-me ATP injection in the arterial blood supply of the hindlimb muscles was attenuated following that heating protocol.…”

“…Meanwhile, it is noted that the functions of P2X receptors have also been reported to be altered by temperature in surrounding tissues (Garcia-Villalon et al, 1997;Ziganshin et al, 2002;Kluess et al, 2005). In a recent study, we demonstrated that the repeated heat exposure protocol [increasing ~1.5°C of muscle temperature (Tm) for 30 min, two times per day for three continuous days] effectively suppresses the P2X 3 expression and attenuates the BP response to muscle contraction in rats with simulated PAD (Qin et al, 2020). Nonetheless, it is also necessary to determine a short-period of heating intervention relieving the symptoms of intermittent claudication.…”

“…Our previous study (Liu et al, 2011) also indicated that the P2X 3 expression in the DRG was not upregulated at 6 h but started to increase 24 h following the femoral artery ligation. Likewise, the attenuation of the exaggerated P2X 3 expression in the DRG of PAD rats also requires a time course, as shown that there was 3 h of accumulated heating exposure in the previous repeated heating protocol (Qin et al, 2020). Moreover, during the repeated heating treatment, half of the heating procedures were already completed during the first 24 h following the ligation, which was before P2X 3 upregulation.…”