Celiprolol inhibits mitogen-activated protein kinase and endothelin-1 and transforming growth factor-beta(1) gene in rats

We evaluated the cardioprotective effects of long-term treatment with celiprolol (for 5 weeks), a specific beta(1)-adrenoceptor antagonist with a weak beta(2)-adrenoceptor agonist action, on endothelin-1 and transforming growth factor (TGF)-beta(1) expression and cardiovascular remodeling in deoxyco...

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Bibliographic Details
Published in:European journal of pharmacology 2002-12, Vol.457 (2-3), p.85-93
Main Authors: Tsubokou, Yusuke, Kobayashi, Naohiko, Mita, Shin-ichiro, Yoshida, Kohtaro, Matsuoka, Hiroaki
Format: Article
Language:English
Subjects:
Adrenergic beta-Antagonists - pharmacology
Animals
Blotting, Western
Body Weight - drug effects
Celiprolol - pharmacology
Desoxycorticosterone
Endothelin-1 - antagonists & inhibitors
Endothelin-1 - biosynthesis
Gene Expression Regulation - drug effects
Heart Ventricles - drug effects
Heart Ventricles - metabolism
Heart Ventricles - pathology
Hemodynamics - drug effects
Hypertension - enzymology
Hypertension - metabolism
Hypertension - physiopathology
Male
Mitogen-Activated Protein Kinases - antagonists & inhibitors
Mitogen-Activated Protein Kinases - biosynthesis
Organ Size - drug effects
Rats
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
Signal Transduction - drug effects
Transforming Growth Factor beta - biosynthesis
Transforming Growth Factor beta - genetics
Transforming Growth Factor beta1
Ventricular Remodeling - drug effects
Ventricular Remodeling - physiology
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Summary:We evaluated the cardioprotective effects of long-term treatment with celiprolol (for 5 weeks), a specific beta(1)-adrenoceptor antagonist with a weak beta(2)-adrenoceptor agonist action, on endothelin-1 and transforming growth factor (TGF)-beta(1) expression and cardiovascular remodeling in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Upregulated preproendothelin-1, endothelin ET(A) receptor, TGF-beta(1), c-fos, and type I collagen expression and extracellular signal-regulated kinase activities were suppressed by celiprolol. Celiprolol effectively inhibited vascular lesion formation such as medial thickness and perivascular fibrosis. These observations suggested that extracellular signal-regulated kinase and c-fos gene pathway may contribute to the cardiovascular remodeling of DOCA rats, and that cardioprotective effects of celiprolol on cardiovascular remodeling may be mediated, at least in part, by suppressed expression of endothelin-1 and TGF-beta(1).
ISSN:0014-2999
DOI:10.1016/S0014-2999(02)02648-1