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(Circulation Research. 2009;104:228.)
© 2009 American Heart Association, Inc.

Integrative Physiology

Cyclooxygenase-2–Derived Prostaglandin F₂ Mediates Endothelium-Dependent Contractions in the Aortae of Hamsters With Increased Impact During Aging

Siu Ling Wong, Fung Ping Leung, Chi Wai Lau, Chak Leung Au, Lai Ming Yung, Xiaoqiang Yao, Zhen-Yu Chen, Paul M. Vanhoutte, Maik Gollasch, Yu Huang

From the Institute of Vascular Medicine (S.L.W., F.P.L., X.Y., Z.-Y.C., Y.H.) and Departments of Physiology (S.L.W., F.P.L., C.W.L., C.L.A., L.M.Y., X.Y., Y.H.) and Biochemistry (Z.-Y.C.), Chinese University of Hong Kong, China; Department of Pharmacology (P.M.V.), University of Hong Kong, China; and Medical Clinic for Nephrology and Internal Intensive Care (M.G.), Charité University Medicine Berlin, Germany.

Correspondence to Yu Huang, PhD, Department of Physiology, Chinese University of Hong Kong, Shatin, NT, Hong Kong. E-mail yu-huang{at}cuhk.edu.hk

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 ([Ca²⁺]_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 [Ca²⁺]_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)F₂ and prostacyclin (PGI₂) increased by ACh; only PGF₂ caused contraction at relevant concentrations. COX-2 expression, ACh-stimulated contractions, and vascular sensitivity to PGF₂ were augmented in aortae from aged hamsters. Human renal arteries also showed thromboxane–prostanoid receptor–mediated ACh- or PGF₂-induced contractions and COX-2–dependent release of PGF₂. The present study demonstrates that PGF₂, 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 [Ca²⁺]_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.

Key Words: endothelium-derived contracting factors • cyclooxygenase-2 • thromboxane-prostanoid receptor • aging • aorta

Related Article:

Cyclooxygenase-2-Derived Prostaglandin F₂: An Endothelium-Derived Contractile Factor Acting Independently of Other Endothelium-Derived Contractile Factors via Vascular Thromboxane Receptors

Karsten Schrör
Circ. Res. 2009 104: 141-143. [Extract] [Full Text] [PDF]

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