PPADS does not block contraction-induced prostaglandin E2 synthesis in cat skeletal muscle

Abstract

Pyridoxal-phosphate-6-azophenyl-2'-4-disulfonate (PPADS), a purinergic 2 (P2) receptor antagonist, has been shown to attenuate the exercise pressor reflex in cats. In vitro, however, PPADS has been shown to block the production of prostaglandins, some of which play a role in evoking the exercise pressor reflex. Thus the possibility exists that PPADS blocks the exercise pressor reflex through a reduction in prostaglandin synthesis rather than through the blockade of P2 receptors. Using microdialysis, we collected interstitial fluid from skeletal muscle to determine prostaglandin E2 (PGE2) concentrations during the intermittent contraction of the triceps surae muscle before and after a popliteal arterial injection of PPADS (10 mg/kg). We found that the PGE2 concentration increased in response to the intermittent contraction before and after the injection of PPADS (both, P < 0.05). PPADS reduced the pressor response to exercise (P < 0.05) but had no effect on the magnitude of PGE2 production during contraction (P = 0.48). These experiments demonstrate that PPADS does not block the exercise pressor reflex through a reduction in PGE2 synthesis. We suggest that PGE2 and P2 receptors play independent roles in stimulating the exercise pressor reflex.

Fig. 1.

Effects of intermittent static contraction on prostaglandin E₂ concentrations ([PGE₂]) before and after injection of pyridoxal-phosphate-6-azophenyl-2′-4-disulfonate (PPADS; A), indomethacin (B), or saline (C). White bars represent baseline values, and black bars represent values during contraction. *P < 0.05 baseline vs. peak. The symbol + indicates that PGE₂ concentration during contraction after indomethacin was significantly less (P = 0.005) than PGE₂ concentration during contraction before indomethacin (i.e., control). Horizontal bracket signifies that the increase in PGE₂ concentration after indomethacin was significantly less (P = 0.009) than the increase in PGE₂ concentration before indomethacin (i.e., control). n, Number of cats.