Cyclooxygenase-2 Selectively Controls Renal Blood Flow Through a Novel PPARβ/δ-Dependent Vasodilator Pathway.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_F72671819252
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Cyclooxygenase-2 Selectively Controls Renal Blood Flow Through a Novel PPARβ/δ-Dependent Vasodilator Pathway.
Périodique
Hypertension
Auteur(s)
Kirkby N.S., Sampaio W., Etelvino G., Alves D.T., Anders K.L., Temponi R., Shala F., Nair A.S., Ahmetaj-Shala B., Jiao J., Herschman H.R., Wang X., Wahli W., Santos R.A., Mitchell J.A.
ISSN
1524-4563 (Electronic)
ISSN-L
0194-911X
Statut éditorial
Publié
Date de publication
02/2018
Peer-reviewed
Oui
Volume
71
Numéro
2
Pages
297-305
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Cyclooxygenase-2 (COX-2) is an inducible enzyme expressed in inflammation and cancer targeted by nonsteroidal anti-inflammatory drugs. COX-2 is also expressed constitutively in discreet locations where its inhibition drives gastrointestinal and cardiovascular/renal side effects. Constitutive COX-2 expression in the kidney regulates renal function and blood flow; however, the global relevance of the kidney versus other tissues to COX-2-dependent blood flow regulation is not known. Here, we used a microsphere deposition technique and pharmacological COX-2 inhibition to map the contribution of COX-2 to regional blood flow in mice and compared this to COX-2 expression patterns using luciferase reporter mice. Across all tissues studied, COX-2 inhibition altered blood flow predominantly in the kidney, with some effects also seen in the spleen, adipose, and testes. Of these sites, only the kidney displayed appreciable local COX-2 expression. As the main site where COX-2 regulates blood flow, we next analyzed the pathways involved in kidney vascular responses using a novel technique of video imaging small arteries in living tissue slices. We found that the protective effect of COX-2 on renal vascular function was associated with prostacyclin signaling through PPARβ/δ (peroxisome proliferator-activated receptor-β/δ). These data demonstrate the kidney as the principle site in the body where local COX-2 controls blood flow and identifies a previously unreported PPARβ/δ-mediated renal vasodilator pathway as the mechanism. These findings have direct relevance to the renal and cardiovascular side effects of drugs that inhibit COX-2, as well as the potential of the COX-2/prostacyclin/PPARβ/δ axis as a therapeutic target in renal disease.
Mots-clé
Animals, Cyclooxygenase 2/metabolism, Cyclooxygenase Inhibitors/pharmacology, Kidney/blood supply, Kidney/metabolism, Mice, PPAR delta/metabolism, PPAR-beta/metabolism, Renal Circulation/drug effects, Signal Transduction/drug effects, cyclooxygenase 2, endothelium, inflammation, regional blood flow, spleen
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/02/2018 8:38
Dernière modification de la notice
20/08/2019 17:23
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