Cyclooxygenase-2-derived prostaglandin F(2α) mediates endothelium-dependent contractions in the aortae of hamsters with increased impact during aging

Item Type:	Article
Title:	Cyclooxygenase-2-derived prostaglandin F(2α) mediates endothelium-dependent contractions in the aortae of hamsters with increased impact during aging
Creators Name:	Wong, S.L. and Leung, F.P. and Lau, C.W. and Au, C.L. and Yung, L.M. and Yao, X. and Chen, Z.Y. and Vanhoutte, P.M. and Gollasch, M. and Huang, Y.
Abstract:	Hypertension and vascular dysfunction result in the increased release of endothelium-derived contracting factors (EDCFs), whose identity is poorly defined. We tested the hypothesis that endothelial cyclooxygenase (COX)-2 can generate EDCFs and identified the possible EDCF candidate. Changes in isometric tension of aortae of young and aged hamsters were recorded on myograph. Real-time changes in intracellular calcium concentrations ([Ca(2+)](i)) in native aortic endothelial cells were measured by imaging. Endothelium-dependent contractions were triggered by acetylcholine (ACh) after inhibition of nitric oxide production and they were abolished by COX-2 but not COX-1 inhibitors or by thromboxane-prostanoid receptor antagonists. 2-Aminoethoxydiphenyl borate (cation channel blocker) eliminated endothelium-dependent contractions and ACh-stimulated rises in endothelial cell [Ca(2+)](i). RT-PCR and Western blotting showed COX-2 expression mainly in the endothelium. Enzyme immunoassay and high-performance liquid chromatography-coupled mass spectrometry showed release of prostaglandin (PG)F(2{alpha}) and prostacyclin (PGI(2)) increased by ACh; only PGF(2{alpha}) caused contraction at relevant concentrations. COX-2 expression, ACh-stimulated contractions, and vascular sensitivity to PGF(2{alpha}) were augmented in aortae from aged hamsters. Human renal arteries also showed thromboxane-prostanoid receptor-mediated ACh- or PGF(2{alpha})-induced contractions and COX-2-dependent release of PGF(2{alpha}). The present study demonstrates that PGF(2{alpha}), derived from COX-2, which is localized primarily in the endothelium, is the most likely EDCF underlying endothelium-dependent, thromboxane-prostanoid receptor-mediated contractions to ACh in hamster aortae. These contractions involved increases in endothelial cell [Ca(2+)](i). The results support a critical role of COX-2 in endothelium-dependent contractions in this species with an increased importance during aging and, possibly, a similar relevance in humans.
Keywords:	Aging, Aorta, Cyclooxygenase-2, Endothelium-Derived Contracting Factors, Thromboxane-Prostanoid Receptor, Animals, Cricetinae
Source:	Circulation Research
ISSN:	0009-7330
Publisher:	American Heart Association
Volume:	104
Number:	2
Page Range:	228-235
Date:	30 January 2009
Official Publication:	https://doi.org/10.1161/CIRCRESAHA.108.179770
PubMed:	View item in PubMed

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