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

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 PGE ₂ synthesis. We suggest that PGE₂ and P₂ receptors play independent roles in stimulating the exercise pressor reflex.