Gap junction remodeling in hypertrophied left ventricles of aortic-banded rats: prevention by angiotensin II type 1 receptor blockade.
Remodeling of gap-junctional organization in hypertrophied left ventricle (LV) in response to pressure overload in rats induced by abdominal aorta banding was investigated by immunoconfocal and electron microscopy. Eight to 12 weeks after banding, rats developed significant LV hypertrophy. In contrast to control LV myocytes, which showed connexin43 (Cx43) labeling largely confined to the intercalated disks, LV myocytes from aortic-banded rats showed dispersion of punctate Cx43 labeling over the entire cell surface. In LV tissues sectioned longitudinally, the proportion of Cx43 label at the intercalated disk decreased significantly (control, 0.87 v aortic-banded, 0.62). En-face views of intercalated disks of hypertrophied myocardium revealed a reduction of Cx43 gap junctions in the disk center, giving rise to a significant decrease in the proportion of the disk occupied by gap-junctional membrane (control, 0.32 v aortic-banded, 0.24). Electron microscopy of hypertrophied LV tissue revealed that Cx43-containing gap junctions were frequently displaced from their usual locations to form side-to-side contacts distant from the disk, and also appeared as annular profiles. In aortic-banded rats treated with the angiotensin II (AII) type 1 receptor (AT1) antagonist, losartan (10 mg/kg/day, 11 weeks) not only LV hypertrophy, but also the gap junction disorganization was markedly reduced. These results suggest that LV hypertrophy induced by pressure overload is associated with Cx43 gap junction disorganization and that AII may play an important role either directly or indirectly in gap-junctional remodeling.
Emdad
L
L
Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Uzzaman
M
M
Takagishi
Y
Y
Honjo
H
H
Uchida
T
T
Severs
N J
NJ
Kodama
I
I
Murata
Y
Y
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001011:Aorta / Q000378:metabolism*; D015153:Blotting, Western; D018031:Connexin 43 / Q000096:biosynthesis; D003896:Desmosomes / Q000378:metabolism; D017629:Gap Junctions / Q000473:pathology / Q000648:ultrastructure; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D019808:Losartan / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013997:Time Factors
D057911:Angiotensin Receptor Antagonists; D000889:Anti-Arrhythmia Agents; D018031:Connexin 43; D011945:Receptors, Angiotensin; D019808:Losartan