title: Fibrotic response to angiotensin II is blunted in the kidney, but not in the heart, in insulin-sensitive long-lived transgenic dwarf rats.
abstract: 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.
authors.affiliation: Division of Cardiovascular Medicine, Course of Medical and Dental Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Osami
authors.initials: O
authors.lastname: Sato
authors.forename: Naoto
authors.initials: N
authors.lastname: Ashizawa
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtsuru
authors.forename: Ryo
authors.initials: R
authors.lastname: Imanishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kawano
authors.forename: Shinji
authors.initials: S
authors.lastname: Seto
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Isao
authors.initials: I
authors.lastname: Shimokawa
authors.forename: Katsusuke
authors.initials: K
authors.lastname: Yano
mesh_terms: 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
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I