Effect of muscle interstitial pH on P2X and TRPV1 receptors‐mediated pressor response

Previous studies show that activation of purinergic P2X receptors and transient receptor potential vanilloid type 1 (TRPV1) located on muscle afferent nerve evokes a pressor response. P2X and TRPV1 receptors are also sensitive to changes in pH. The aim of this study was to examine the effect of decreasing interstitial pH on the pressor reflex mediated by those receptors in skeletal muscle. In decerebrated rats, interstitial pH in the triceps surae muscle was adjusted by infusing Ringer solutions at pH: 4.5, 5.5, 6.5 and 7.4 into the femoral artery. Interstitial samples were collected using microdialysis probes inserted into the muscles and pH was measured. Arterial injection ofα, β‐methylene ATP (0.25 mM), a P2X agonist, at pH values of 7.4, 6.5 and 5.5 increased mean arterial pressure (MAP) by 29±2, 24±3 and 21±3 mmHg ( P <0.05 for 5.5 vs. pH 7.4) respectively. Capsaicin (1μg/kg TRPV1 agonist) injected into the artery at pH 7.4, 6.5, 5.5 and 4.5 elevated MAP by 29±4, 33±2, 35±3 and 40±3 mmHg ( P <0.05 for 4.5 vs. pH 7.4) respectively. Our data indicate that skeletal muscle acidosis attenuates P2X receptor‐mediated responses; but enhances TRPV1 receptor‐mediated response. Exaggerated TRPV1 response requires lower pH in muscle. This study provides evidence that muscle pH may be important in modulating P2X and TRPV1 responsiveness in exercising muscle. Supported by R01 HL075533 , R01 HL078866 (Li) and R01 HL060800 (Sinoway).