Effects of cyclooxygenase-1 and -2 inhibition on gastric acid secretion and cardiovascular functions in rats.
The discovery of a second isoform of cyclooxygenase has led to a re-evaluation of the mechanisms underlying the adverse effects of nonsteroidal anti-inflammatory drugs, focusing in particular on the gastrointestinal system. We investigated the involvement of cyclooxygenase-1 and -2 in the regulation of gastric acid secretion and cardiovascular functions in anesthetized rats, after acute intravenous administration of the selective cyclooxygenase-1 inhibitor SC-560, the selective cyclooxygenase-2 inhibitor celecoxib and the nonselective inhibitor indomethacin. Indomethacin, celecoxib and SC-560 did not significantly modify basal acid secretion. Indomethacin and celecoxib were also ineffective on the acid secretion stimulated by pentagastrin; by contrast, SC-560 significantly enhanced the acid secretion stimulated by pentagastrin, electrical vagal stimulation or histamine. The stimulatory effects of SC-560 were prevented by cervical vagotomy, atropine and famotidine. Indomethacin caused either no change, increasing or decreasing effects on mean arterial pressure and heart rate. By contrast, SC-560 was unable to change cardiovascular parameters at 5 mg/kg, while inducing a marked bradycardia at 10 mg/kg. Celecoxib was ineffective. Our findings indicate that cyclooxygenase-1-derived prostaglandins are involved in the regulation of stimulated acid secretion and of basal heart rate; the role of prostaglandins in the acute control of systemic blood pressure under resting conditions seems to be negligible.
Adami
Maristella
M
Department of Human Anatomy, Pharmacology and Forensic Medicine, Section of Pharmacology, University of Parma, Via Volturno 39, IT-43100 Parma, Italy.
Coppelli
Gabriella
G
Guaita
Elena
E
Pozzoli
Cristina
C
Menozzi
Alessandro
A
Giovannini
Elena
E
Coruzzi
Gabriella
G
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D000068579:Celecoxib; D051545:Cyclooxygenase 1 / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D005744:Gastric Acid / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D007213:Indomethacin / Q000009:adverse effects; D008297:Male; D010418:Pentagastrin / Q000009:adverse effects; D011720:Pyrazoles / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000009:adverse effects; D014628:Vagotomy
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D010418:Pentagastrin; D000068579:Celecoxib; D007213:Indomethacin