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 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).
Tsubokou
Yusuke
Y
Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan
Kobayashi
Naohiko
N
Mita
Shin-ichiro
S
Yoshida
Kohtaro
K
Matsuoka
Hiroaki
H
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D017272:Celiprolol / Q000494:pharmacology*; D003900:Desoxycorticosterone; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D019332:Endothelin-1; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003900:Desoxycorticosterone; D017272:Celiprolol; D020928:Mitogen-Activated Protein Kinases