Involvement of cyclooxygenase 2 in the protective effect of 17beta-estradiol on hypercholesterolemic rabbit aorta.
The involvement of cyclooxygenase (COX) in the effects of 17beta-estradiol was investigated on hypercholesterolemic rabbits aorta. Acetylsalycilic acid, nimesulide, or SQ22536 was used as respective antagonist of COX-1, COX-2, or adenylate cyclase using aortic rings precontracted with phenylephrine and exposed to cumulative concentrations of acetylcholine (ACh). The relaxation effect of ACh was impaired by hypercholesterolemia and restored by an 8-week 17beta-estradiol treatment. In the control group treated with estrogen, nimesulide, acetylsalycilic acid, or SQ22536 slightly reduced the response to ACh. In hypercholesterolemic rabbits treated with estrogen, nimesulide significantly reduced the maximal relaxation and shifted to the right the relaxation curve of ACh, whereas acetylsalycilic acid did not modify the maximal response to ACh but displaced slightly the concentration-response curve. SQ22536 reduced the relaxant effect of ACh down to the level obtained in the presence of nimesulide. These results suggest that the protective effect of 17beta-estradiol against hypercholesterolemia involved COX-2/adenylate cyclase pathway.
Ghanam
K
K
Faculté de Pharmacie, Laboratoire de Pharmacologie, 2, rue du Dr Marcland, Limoges Cedex, 87025, France. ghanam@hotmail.com
Lavagna
C
C
Burgaud
J L
JL
Javellaud
J
J
Ea-Kim
L
L
Oudart
N
N
D000109:Acetylcholine / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology; D001241:Aspirin / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000097:blood / Q000201:enzymology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D013449:Sulfonamides; D014280:Triglycerides; C017759:9-(tetrahydro-2-furyl)-adenine; D004958:Estradiol; D002784:Cholesterol; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000225:Adenine; D000109:Acetylcholine; D001241:Aspirin; C012655:nimesulide; D007213:Indomethacin