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p38 MAPK contributes to angiotensin II-induced COX-2 expression in aortic fibroblasts from normotensive and hypertensive rats.

Authors :
Beltrán AE
Briones AM
García-Redondo AB
Rodríguez C
Miguel M
Alvarez Y
Alonso MJ
Martínez-González J
Salaices M
Source :
Journal of hypertension [J Hypertens] 2009 Jan; Vol. 27 (1), pp. 142-54.
Publication Year :
2009

Abstract

Objective: To investigate the effect of angiotensin II on cyclooxygenase-2 (COX-2) expression in aortic adventitial fibroblasts from normotensive [Wistar-Kyoto (WKY)] rats and spontaneously hypertensive rats (SHRs).<br />Methods: Protein expression was determined by western blot, mRNA levels by real-time PCR, transcriptional activity by luciferase assays, superoxide anion (O2*-) production by dihydroethidine fluorescence and prostaglandin E2 by enzyme immunoassay.<br />Results: Angiotensin II (0.1 micromol/l, 0.5-6 h) time dependently induced COX-2 protein expression, this effect being transient in fibroblasts from WKY rats and maintained over time in SHRs. Angiotensin II effect was abolished by valsartan (1 micromol/l), an angiotensin II type 1 receptor antagonist. Angiotensin II-induced prostaglandin E2 production was reduced by valsartan and the COX-2 inhibitor NS398 (1 micromol/l). Angiotensin II increased O2*- production more in SHR than WKY rats. This increase was reduced by apocynin (30 micromol/l) and allopurinol (10 micromol/l), respective nicotinamide adenine dinucleotide phosphate (NADPH) and xanthine oxidase inhibitors. However, angiotensin II-induced COX-2 expression was unaffected by apocynin, allopurinol, tempol (1 mmol/l) or catalase (1000 U/ml). Angiotensin II (2-30 min) induced p38 mitogen-activated protein kinase (MAPK) phosphorylation, transiently in WKY rats but sustained in SHRs. The p38 inhibitor SB203580 (10 micromol/l) reduced angiotensin II-induced COX-2 protein and mRNA levels. The angiotensin II effect was not prevented by inhibition of mRNA synthesis, and angiotensin II was unable to modulate COX-2 transcriptional activity.<br />Conclusions: Angiotensin II increases COX-2 expression in aortic fibroblasts through mechanisms including p38 MAPK pathway, independent of reactive oxygen species production and nonmediated by COX-2 transcriptional activity modulation. The sustained angiotensin-induced p38 MAPK activation in SHR cells might be related to the maintained COX-2 expression in this strain.

Details

Language :
English
ISSN :
0263-6352
Volume :
27
Issue :
1
Database :
MEDLINE
Journal :
Journal of hypertension
Publication Type :
Academic Journal
Accession number :
19145780
Full Text :
https://doi.org/10.1097/hjh.0b013e328317a730