Document Detail


Pioglitazone treatment increases COX-2-derived prostacyclin production and reduces oxidative stress in hypertensive rats: role in vascular function.
MedLine Citation:
PMID:  22220498     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: PPARγ agonists, glitazones, have cardioprotective and anti-inflammatory actions associated with gene transcription interference. In this study, we determined whether chronic treatment of adult spontaneously hypertensive rats (SHR) with pioglitazone alters BP and vascular structure and function, and the possible mechanisms involved.
EXPERIMENTAL APPROACH: Mesenteric resistance arteries from untreated or pioglitazone-treated (2.5 mg·kg⁻¹ ·day⁻¹ , 28 days) SHR and normotensive [Wistar Kyoto (WKY)] rats were used. Vascular structure was studied by pressure myography, vascular function by wire myography, protein expression by Western blot and immunohistochemistry, mRNA levels by RT-PCR, prostanoid levels by commercial kits and reactive oxygen species (ROS) production by dihydroethidium-emitted fluorescence.
KEY RESULTS: In SHR, pioglitazone did not modify either BP or vascular structural and mechanical alterations or phenylephrine-induced contraction, but it increased vascular COX-2 levels, prostacyclin (PGI₂) production and the inhibitory effects of NS 398, SQ 29,548 and tranylcypromine on phenylephrine responses. The contractile phase of the iloprost response, which was reduced by SQ 29,548, was greater in pioglitazone-treated and pioglitazone-untreated SHR than WKY. In addition, pioglitazone abolished the increased vascular ROS production, NOX-1 levels and the inhibitory effect of apocynin and allopurinol on phenylephrine contraction, whereas it did not modify eNOS expression but restored the potentiating effect of N-nitro-L-arginine methyl ester on phenylephrine responses.
CONCLUSIONS AND IMPLICATIONS: Although pioglitazone did not reduce BP in SHR, it increased COX-2-derived PGI₂ production, reduced oxidative stress, and increased NO bioavailability, which are all involved in vasoconstrictor responses in resistance arteries. These effects would contribute to the cardioprotective effect of glitazones reported in several pathologies.
Authors:
Raquel Hernanz; Ángela Martín; Jose V Pérez-Girón; Roberto Palacios; Ana M Briones; Marta Miguel; Mercedes Salaices; María J Alonso
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  166     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-18     Completed Date:  2012-10-09     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1303-19     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
Affiliation:
Departamento de Bioquímica, Fisiología y Genética Molecular, Universidad Rey Juan Carlos, Alcorcón, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antihypertensive Agents / therapeutic use
Cyclooxygenase 2 / genetics,  metabolism*
Cyclooxygenase Inhibitors / pharmacology
Epoprostenol / metabolism*
Gene Expression Regulation, Enzymologic / drug effects
Hypertension / drug therapy*,  metabolism,  physiopathology
Male
Mesenteric Arteries / drug effects*,  metabolism,  physiopathology
Nitric Oxide / metabolism
Oxidative Stress / drug effects*
PPAR gamma / agonists*,  genetics,  metabolism
RNA, Messenger / metabolism
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Reactive Oxygen Species / metabolism
Thiazolidinediones / therapeutic use*
Up-Regulation / drug effects
Vasodilation / drug effects
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Cyclooxygenase Inhibitors; 0/PPAR gamma; 0/RNA, Messenger; 0/Reactive Oxygen Species; 0/Thiazolidinediones; 10102-43-9/Nitric Oxide; 35121-78-9/Epoprostenol; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/Ptgs2 protein, rat; X4OV71U42S/pioglitazone
Comments/Corrections

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