Cardiovascular Research Advance Access first published online on October 24, 2008
This version [Corrected Proof] published online on November 16, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn287
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Selective cyclooxygenase-2 inhibition directly increases human vascular reactivity to norepinephrine during acute inflammation
1 INSERM U698: Haemostasis, Bio-engineering and Cardiovascular Remodeling, CHU X. Bichat, 46, rue Henri Huchard, Paris 75018, France
2 Paris XIII University, Villetaneuse 93430, France
* Corresponding author. Tel: +33 1 40257529; fax: +33 1 40258602. E-mail address: xnorel{at}hotmail.com
Aims: The use of cyclooxygenase-2 (COX-2) inhibitors has been reported to be associated with detrimental vascular events. The aim of our study was to evaluate the role of COX-2 activity in the control of human vascular tone under inflammatory conditions.
Methods and results: Using organ bath experiments, the contraction induced by norepinephrine (NE), U46619
[GenBank]
, acetylcholine, and KCl was performed on isolated human internal mammary arteries (IMA) cultured in the presence or absence of both interleukin-1β (IL-1β) and lipopolysaccharide (LPS) with or without endothelium. Under these conditions the COX (cyclooxygenase) isoforms were detected by immunohistochemistry and western blot, and the prostaglandins (PG) and thromboxane (Tx) released were measured using an enzyme immunoassay kit. A significant decrease in the maximal effect induced by NE but not by other stimuli was observed in the IL-1β- and LPS-treated preparations after 6 and 24 h of culture (–19 ± 6 and –25 ± 4%, respectively), an effect that was endothelium independent. Under this inflammatory condition, the COX-2 inhibitors DFU (1 µmol/L), DuP-697 (0.5 µmol/L), and Etoricoxib (1 µmol/L) markedly restored and increased the vascular reactivity to NE. These alterations were not observed with SC-560 (1 µmol/L), a selective COX-1 inhibitor. In addition, the COX-1 isoform was always detected and the COX-2 isoform was only found in human IMA exposed for 6 or 24 h under inflammatory conditions. The COX-2 induction was accompanied by an increase in PGE2 (prostaglandin E2) and PGI2 (prostaglandin I2) release in the culture medium (
2.5-fold) but not with an increase in TxA2 (thromboxane A2) release.
Conclusion: These observations suggest that the inhibition of COX-2 directly potentiates the human vascular tone induced by NE under inflammatory conditions.
KEYWORDS Vascular tone; COX-2 inhibitors; Human internal mammary arteries; Vasoconstriction; Prostaglandins
Time for primary review: 17 days
Related Article
CiteULike 
Connotea 
Del.icio.us What's this?
Cardiovasc Res 2009 81: 240-241.
This article has been cited by other articles:
|
|
 |
|
  N. Foudi, X. Norel, M. Rienzo, L. Louedec, C. Brink, J.-B. Michel, and M. Back Altered reactivity to norepinephrine through COX-2 induction by vascular injury in hypercholesterolemic rabbits Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1882 - H1888. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Krotz Putting the vasoactive effects of COX-2-derived prostanoids into clinical perspective Cardiovasc Res, February 1, 2009; 81(2): 240 - 241. [Full Text] [PDF]
|
|