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

McCord JL, Hayes SG, Kaufman MP. PPADS does not block contraction- induced prostaglandin E-2 synthesis in cat skeletal muscle. Am J Physiol Heart Circ Physiol 295: H2043-H2045, 2008. First published September 12, 2008; doi:10.1152/ajpheart.00904.2008. Pyridoxal-phosphate-6-azophenyl-2'-4-disulfonate (PPADS), a purinergic 2 (P-2) 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 P-2 receptors. Using microdialysis, we collected interstitial fluid from skeletal muscle to determine prostaglandin E-2 (PGE(2)) 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 PGE(2) 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 PGE(2) production during contraction (P = 0.48). These experiments demonstrate that PPADS does not block the exercise pressor reflex through a reduction in PGE(2) synthesis. We suggest that PGE(2) and P-2 receptors play independent roles in stimulating the exercise pressor reflex.