Fibrotic response to angiotensin II is blunted in the kidney, but not in the heart, in insulin-sensitive long-lived transgenic dwarf rats.
Insulin resistance is a characteristic feature of cardiovascular and renal diseases, and angiotensin II (Ang II) has been suggested to induce insulin resistance. The aims of this study were to elucidate the effect of chronic Ang II infusion on vascular reactivity and organ damage in insulin-sensitive rats. We confirmed the following three points. First, there was no significant difference in pressor response to chronic Ang II infusion (600 ng/kg/min) between insulin-sensitive transgenic rats (Tg) and control rats (C). Second, there was no significant difference in cardiac hypertrophy and fibrosis by chronic Ang II infusion between the two groups. However, third, fibrotic response to chronic Ang II infusion evaluated by histopathological scoring in the kidney was significantly decreased in insulin-sensitive transgenic rats (renal fibrosis and nephropathy score: C+Ang II vs Tg+Ang II; 2.5 vs 1.3; p<0.05). Furthermore, the expression of TGF-beta, a fibrosis indicator, was also significantly suppressed in the kidneys of the transgenic rats (TGF-beta1/GAPDH ratio: C+Ang II vs Tg+Ang II; 1.15 vs 0.81; p<0.05). This result indicates that the growth hormone/insulin-like growth factor-1 axis is critically involved in the development of renal injury and fibrosis, rather than hypertension, cardiac hypertrophy, and cardiac fibrosis induced by chronic Ang II administration.
Sato
Osami
O
Division of Cardiovascular Medicine, Course of Medical and Dental Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Ashizawa
Naoto
N
Ohtsuru
Akira
A
Imanishi
Ryo
R
Kawano
Hiroaki
H
Seto
Shinji
S
Yamashita
Shunichi
S
Shimokawa
Isao
I
Yano
Katsusuke
K
D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D030801:Animals, Genetically Modified; D001835:Body Weight / Q000187:drug effects; D004392:Dwarfism; D004452:Echocardiography; D005355:Fibrosis / Q000209:etiology* / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000473:pathology*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D007328:Insulin; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I