[Frontiers in Bioscience E2, 441-448, January 1, 2010]

The influence of constitutive cox-2 in smooth muscle tissue on the contractile effect of phenylephrine in the rat abdominal aorta

Maria del Carmen Castillo-Hernandez1, Gustavo Guevara-Balcazar1, Pedro Lopez-Sanchez1, Juan Asbun-Bojalil2, Enrique Castillo-Henkel1, Carlos Castillo-Henkel2

1Departamento de Posgrado e Investigacion, Escuela Superior de Medicina ,Instituto Politecnico Nacional, Mexico, City, CP 11340, 2Instituto Nacional de Perinatologia, Mexico, City, CP, 11000

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Material and methods
3.1. Preparation of aortic rings and measurement of tension
3.2. Phenylephrine concentration-response curves of thoracic and abdominal aortic rings in the presence or absence of different antagonists
3.3. COX-1 and COX-2 Immunoblot
3.4. Drugs
3.5. Data and statistical analysis
4. Results
4.1. Phenylephrine concentration-response curves in aortic rings without endothelium in thoracic and abdominal aorta
4.2. The effect of indomethacin on the contractile response to phenylephrine
4.3. The effect of SC-560 on the contractile response to phenylephrine
4.4. The effect of NS 398 on the contractile response to phenylephrine
4.5. Immunoblot analysis of COX-1 and COX-2
4.6. An evaluation of the effect of cycloheximide on the contractile response to phenylephrine
4.7. The effect of AATFMK and MAFP on the contractile response to phenylephrine
4.8. The effects of U73122 and RHC80267 on the contractile response to phenylephrine
5. Discussion
6. Acknowledgments
7. References

1. ABSTRACT

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.