Potentiation by cyclooxygenase inhibitors of the release of catecholamines from the rabbit carotid body and its reversal by prostaglandin E2.
Salicylates, at the high therapeutic doses used in the treatment of rheumatoid arthritis, produce an increase in ventilation and augment the carotid body reactivity to hypoxic stimulus, leading to an exaggerated hyperventilation during hypoxia. These effects had been related to the action of salicylates as uncouplers of oxidative phosphorylation. In the present study, carried out in an in vitro preparation of the rabbit carotid body, we show that acetylsalicylic acid and indomethacin, two anti-inflammatory drugs that are also powerful inhibitors of cyclooxygenase, the prostaglandin-synthetizing enzyme, produce an increase in the [3H]catecholamine release evoked by low oxygen stimulation. The drugs did not affect basal normoxic release, a finding that suggests that at the concentration used these anti-inflammatory agents do not have uncoupling actions, and that their effects on hypoxic-induced release of [3H]catecholamines is mediated by their specific action as cyclooxygenase inhibitors. In agreement with this suggestion we found that prostaglandin E2 completely prevented the effects of both anti-inflammatory agents. In addition, our data indicate that endogenously synthetized prostaglandins are powerful modulators of chemoreceptor cell function.
Gómez-Niño
A
A
Departamento de Bioquímica y Biología Molecular y Fisiología, Facultad de Medicina, Universidad de Valladolid, Spain.
Almaraz
L
L
González
C
C
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002344:Carotid Body / Q000187:drug effects / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D011817:Rabbits
D002395:Catecholamines; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D001241:Aspirin; D007213:Indomethacin