Effects of Cyclooxygenase-1 and -2 Inhibition on Gastric Acid Secretion and Cardiovascular Functions in Rats

Abstract

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.

CYCLO‐OXYGENASE‐1 INHIBITION INCREASES ACID SECRETION BY MODULATING H+,K+‐ATPase EXPRESSION AND ACTIVATION IN RABBIT PARIETAL CELLS

“…A decrease in PGE 2 synthesis in parietal cells via COX-1 could potentiate basal and histamine-stimulated gastric acid secretion, as we have observed for non-specific NSAIDs in vitro 8,9 and in vivo. 10,11 Consistent with our latter findings, Adami et al, 36 using the specific COX-1 inhibitor SC-560, have shown that acid secretion is significantly enhanced in secretagogue-stimulated anaesthetized rats. They suggest that COX-1-derived prostaglandin synthesis is involved in the regulation of NSAID-induced gastric acid secretion.…”

Perioperative Use of β-blockers and COX-2 Inhibitors May Improve Immune Competence and Reduce the Risk of Tumor Metastasis

“…The intermediate dose used (10 mg/kg) is often used in rats and was found effective in blocking prostaglandin secretion in an inflammatory model. 17,18 Propranolol-To block β-adrenoceptor stimulation, we used the nonselective β-adrenergic blocker, propranolol (Sigma, Israel). The drug was dissolved in phosphate buffered saline (PBS) and added to a mixture with mineral oil (Sigma, Israel) and mannide monooleate (Arlacel A, Sigma, Israel), in a 4:3:1 ratio, respectively, to create a slowly absorbed emulsion.…”

Effect of Tulbaghia violacea on the blood pressure and heart rate in male spontaneously hypertensive Wistar rats

“…Muscarine (2.5 µg/kg) was then infused into the same animal, after the BP and HR returned to the level prior to the infusion of the MLE. The drugs were infused 20 minutes after atropine infusion (Thán et al, 2000;Dimo et al, 2003;Dabire, 2004;Adami et al, 2006;Ajay et al, 2007; D. Holopherne et al, 2008;Khwanchuea et al, 2008;Lessa et al, 2008;Rattmann et al, 2008;De Menezes et al, 2010).…”