The influence of constitutive COX-2 in smooth muscle tissue on the contractile effect of phenylephrine in the rat abdominal aorta.
Prostanoids are involved in the phenylephrine-induced contraction of the aorta. Here, we examined whether or not constitutive cyclooxygenase-2 (phosholipases C and A2) is the source of prostanoids in the smooth muscle of the arterial wall of the thoracic and abdominal aorta. Both cyclooxygenase isoforms (COX-1 and COX-2) were expressed in the two aortic segments, but their expression was not altered by phenylephrine, the protein synthesis inhibitor cycloheximide, or the phospholipase A2 inhibitors arachidonyl trifluoromethyl ketone and methyl arachidonyl fluorophosponate. Indomethacin and NS398, which are a non-selective and selective COX-2 inhibitor, respectively, but not SC-560, which is a COX-1-selective inhibitor, inhibited the effect of phenylephrine on the abdominal, but not the thoracic, aorta. Similarly, U73122, which is a phospholipase C inhibitor, and RHC80267, which is a diacylglycerol lipase inhibitor, inhibited the effect of phenylephrine. These findings suggest that prostanoids, which are produced by constitutively active COX-2, influence the contractile response of the abdominal aorta and that the production of arachidonic acid relies on phospholipase C and diacylglycerol lipase.
Castillo-Hernandez
Maria Carmen
MC
Departamento de Posgrado e Investigacion, Escuela Superior de Medicina, Instituto Politecnico Nacional, Mexico City, CP 11340.
Guevara-Balcazar
Gustavo
G
Lopez-Sanchez
Pedro
P
Asbun-Bojalil
Juan
J
Lopez
Ruth Mery
RM
Castillo
Enrique Fernando
EF
Castillo-Henkel
Carlos
C
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D015151:Immunoblotting; D007213:Indomethacin / Q000378:metabolism / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009578:Nitrobenzenes / Q000378:metabolism / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D064801:Phospholipase A2 Inhibitors; D011720:Pyrazoles / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D013449:Sulfonamides / Q000378:metabolism / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D064801:Phospholipase A2 Inhibitors; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D010656:Phenylephrine; D003513:Cycloheximide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D010738:Type C Phospholipases; D007213:Indomethacin