Long-term treatment with angiotensin II type 1 receptor antagonist, CV-11974, restores beta-catenin mRNA expression in volume-overloaded rabbit hearts.

Abstract:

:This study aimed to search genes altered in expression after long-term treatment with the angiotensin II type 1 receptor (AT1) antagonist, CV-11974, in volume-overloaded hearts. Arteriovenous shunt was made between the common carotid artery and jugular vein in Japanese White rabbits. Shunt-operated rabbits were randomly treated with CV-11974 or vehicle for 6 weeks, starting 6 weeks after surgery. As controls, sham-operated rabbits were given vehicle. Total RNA was prepared from each left ventricular myocardium. Using differential display, we screened one cDNA encoding human beta-catenin, in which the expression was upregulated after CV-11974 administration in shunt rabbit hearts. Beta-catenin is a molecule that exists in the intercalated disks and also works in cytoplasm as a major component of Wnt signaling. We then examined mRNA expressions of beta-catenin and connexin43 by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The mRNA expressions of beta-catenin and connexin43 were markedly depressed in shunt-operated animals given vehicle compared with sham-operated animals (P < 0.01). These results suggest that downregulation of beta-catenin and connexin43 expression might be involved in the process of ventricular remodeling by volume overload. The RT-PCR also demonstrated that beta-catenin mRNA expression was significantly higher in shunt rabbits treated with CV-11974 than in those given vehicle (P < 0.05). These data suggest that volume overload may downregulate beta-catenin expression by an AT1 receptor-mediated pathway.

journal_name

Heart Vessels

journal_title

Heart and vessels

authors

Itoh M,Takeishi Y,Nakada S,Miyamoto T,Tsunoda Y,Takahashi H,Kubota I,Tomoike H

doi

10.1007/s003800200040

subject

Has Abstract

pub_date

2002-11-01 00:00:00

pages

36-41

issue

1

eissn

0910-8327

issn

1615-2573

journal_volume

17

pub_type

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