Long-term treatment with angiotensin II type 1 receptor antagonist, CV-11974, restores beta-catenin mRNA expression in volume-overloaded rabbit hearts.
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.
Itoh
Makoto
M
First Department of Internal Medicine, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
Takeishi
Yasuchika
Y
Nakada
Shigekazu
S
Miyamoto
Takuya
T
Tsunoda
Yuichi
Y
Takahashi
Hiroki
H
Kubota
Isao
I
Tomoike
Hitonobu
H
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors*; D001562:Benzimidazoles / Q000037:antagonists & inhibitors*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D018031:Connexin 43 / Q000096:biosynthesis / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000187:drug effects*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000187:drug effects; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism* / Q000503:physiopathology; D007564:Japan; D008297:Male; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000187:drug effects*; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000037:antagonists & inhibitors*; D013995:Time; D015534:Trans-Activators / Q000096:biosynthesis* / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects / Q000502:physiology; D051176:beta Catenin
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D018031:Connexin 43; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D015534:Trans-Activators; D051176:beta Catenin; C081643:candesartan