Faculty Collaboration Database

Effect of COX-1/COX-2 inhibition versus selective COX-2 inhibition on coronary vasodilator responses to arachidonic acid and acetylcholine. Pharmacology 2004 Jul;71(3):135-42

Date

05/27/2004

Pubmed ID

15161995

DOI

10.1159/000077447

Scopus ID

2-s2.0-2642525057 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

The effect of a nonselective COX-1/COX-2 inhibitor, naproxen, was compared with a COX-2-selective inhibitor (SC-58236) on coronary vasodilatory responses in the anesthetized dog. Coronary vasodilation was induced by direct intracoronary injection of acetylcholine (ACH) and arachidonic acid (AA) in control animals and in those treated with either naproxen (1, 3, or 10 mg/kg p.o. 24 h prior to the experiment) or SC-58236 (1, 5, or 15 mg/kg p.o. 24 h prior to the experiment). Naproxen, at 10 mg/kg, significantly attenuated the AA-induced vasodilation (prostacyclin dependent) with no effect on ACH-induced vasodilation (nitric oxide dependent). SC-58236 failed to attenuate either AA- or ACH-induced vasodilation. Ex vivo assays were utilized to establish inhibition of COX-2 (lipopolysaccharide-stimulated prostaglandin E2 formation) and COX-1 (serum thromboxane B2) in blood taken from dogs administered 1, 3, or 10 mg/kg naproxen or 15 mg/kg SC-58236. Naproxen (3 and 10 mg/kg) and SC-58236 (15 mg/kg) markedly reduced the lipopolysaccharide-induced prostaglandin E2 formation, whereas SC- 58236 (15 mg/kg) had no effect on serum thromboxane B2. Naproxen significantly reduced thromboxane B2 at all three doses studied. Furthermore, naproxen (10 mg/kg p.o.) significantly inhibited the AA-induced platelet aggregation (thromboxane B2 dependent), whereas SC-58236 had no effect. Collectively, these results demonstrate that SC-58236 is selective for COX-2, while naproxen is a nonselective inhibitor. These data also suggest that vasodilatory responses to AA in the dog are primarily COX-1 dependent. Selective COX-2 inhibition does not affect either prostacyclin or nitric oxide mediated vasodilation in the canine coronary circulation.

Author List

Gross GJ, Moore J

MESH terms used to index this publication - Major topics in bold

Acetylcholine
Animals
Arachidonic Acid
Blood Pressure
Coronary Circulation
Cyclooxygenase 1
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Dinoprostone
Dogs
Dose-Response Relationship, Drug
Female
Heart Rate
Isoenzymes
Lipopolysaccharides
Male
Naproxen
Platelet Aggregation
Prostaglandin-Endoperoxide Synthases
Pyrazoles
Sulfonamides
Thromboxane B2
Vasodilation
Vasodilator Agents