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 PGE2 synthesis. We suggest that PGE2 and P2 receptors play independent roles in stimulating the exercise pressor reflex.
McCord
Jennifer L
JL
Pennsylvania State Heart and Vascular Institute, Pennsylvania State University College of Medicine, 500 Univ. Dr., Mail Code H047, C2706, Hershey Medical Ctr., Hershey, PA 17033, USA. jmccord@hmc.psu.edu
Hayes
Shawn G
SG
Kaufman
Marc P
MP
D000818:Animals; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003655:Decerebrate State; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007269:Injections, Intra-Arterial; D008297:Male; D017551:Microdialysis; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D011150:Popliteal Artery; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D015232:Dinoprostone
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