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Cyclo-oxygenase-1 and -2 contribution to endothelial dysfunction in ageing
1INSERM U-127, Institut Fédératif de Recherche IFR Circulation and University Paris VII, Hôpital Lariboisière, F-75475 Paris cedex 10, France.
British Journal of Pharmacology
|October 13, 2000
Summary
Cyclo-oxygenase (COX) isoforms contribute to endothelial dysfunction in aging. Both COX-1 and COX-2 play active roles in aged rats, impacting vascular responses and prostaglandin release.
Area of Science:
- Vascular Biology
- Aging Research
- Pharmacology
Background:
- Endothelial dysfunction is a hallmark of aging, affecting vascular health.
- Cyclo-oxygenase (COX) enzymes are implicated in regulating vascular tone and inflammation.
- Understanding the specific roles of COX isoforms in aging-related endothelial dysfunction is crucial.
Purpose of the Study:
- To investigate the distinct roles of cyclo-oxygenase-1 (COX-1) and cyclo-oxygenase-2 (COX-2) in endothelial dysfunction observed in aged Wistar rats.
- To compare the functional responses and prostaglandin release in aortic rings from young and aged rats.
- To determine the expression patterns of COX-1 and COX-2 in aortic endothelial cells of young and aged rats.
Main Methods:
- Isometric tension recordings from aortic rings of young and aged rats.
- Pharmacological inhibition of COX-1 and COX-2 isoforms using specific inhibitors (indomethacin, NS-398, valeryl-salicylate) and a thromboxane receptor antagonist (SQ-29548).
- Measurement of acetylcholine (ACh)-stimulated release of prostacyclin, prostaglandin F(2alpha), and thromboxane A(2).
- Immunohistochemical analysis of COX-1 and COX-2 expression in aortic endothelial cells.
Main Results:
- Aged rats exhibited a biphasic response to acetylcholine (relaxation followed by contraction), unlike the pure relaxation in young rats.
- Inhibition of COX-1 and COX-2, along with thromboxane receptor antagonism, modulated the acetylcholine-induced responses in aged rats.
- Aged rats showed altered ACh-stimulated release of prostaglandins and thromboxane A(2) compared to young rats.
- COX-2 expression was detected in aortic endothelial cells of aged rats, while both COX-1 and COX-2 were present in young rats.
Conclusions:
- Both COX-1 and COX-2 actively contribute to endothelial dysfunction associated with aging in Wistar rats.
- Age-related changes in vascular responses are linked to altered prostaglandin synthesis and COX isoform activity.
- Targeting COX pathways may offer therapeutic potential for managing age-related vascular complications.