Submitted on August 18, 2008
Revised on September 5, 2008
Accepted on September 8, 2008
PPADS does not block contraction-induced prostaglandin E2 synthesis in cat skeletal muscle
Jennifer L. McCord1*, Shawn G Hayes1, and Marc P Kaufman1
1 Penn State University
* To whom correspondence should be addressed. E-mail: jmccord{at}hmc.psu.edu.
Pyridoxal-phosphate-6-azophenyl-2'-4-di-sulphonate (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 intermittent contraction of the triceps surae muscle before and after popliteal arterial injection of PPADS (10 mg/kg). We found that PGE2 concentration increased in response to intermittent contraction before and after 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.
