Heme oxygenase-1 is upregulated in the rat heart in response to chronic administration of angiotensin II.
Heme oxygenase (HO) is a heme-catabolizing enzyme that converts heme into biliverdin, iron, and carbon monoxide. HO-1, an inducible form of HO, is thought to act as an endogenous antioxidant defense mechanism. To determine whether chronic administration of angiotensin II affects HO-1 expression in the heart, expression and localization of HO-1 were investigated in the heart of rats receiving angiotensin II infusion (0.7 mg. kg(-1). day(-1)) via osmotic minipump for up to 7 days. Angiotensin II induced formation of granulation tissue, characterized by myofibroblast proliferation, fibrous deposition, and inflammatory cell migration. Angiotensin II also upregulated cardiac HO-1 expression. Immunohistochemistry revealed that HO-1 was intensively expressed in the granulation tissue. The selective AT(1)-receptor antagonist, losartan, completely, but hydralazine only partially, suppressed angiotensin II-induced granulation tissue formation and HO-1 upregulation. Chronic norepinephrine infusion (2.8 mg. kg(-1). day(-1)) did not induce granulation tissue formation or HO-1 upregulation. Our data suggest that angiotensin II upregulates cardiac HO-1 expression in the newly formed inflammatory lesion, which may represent an adaptive response to angiotensin II-induced cardiac damage.
Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Bunkyo-ku, Tokyo 113-8655, Japan. nobuishizka-tky@umin.ac.jp
N
N
Ishizaka
T
T
Aizawa
I
I
Mori
J
J
Taguchi
Y
Y
Yazaki
R
R
Nagai
M
M
Ohno
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006321:Heart / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006830:Hydralazine / Q000494:pharmacology; D007262:Infusions, Intravenous; D007700:Kinetics; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D009638:Norepinephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects
D000959:Antihypertensive Agents; D012333:RNA, Messenger; D000804:Angiotensin II; D006830:Hydralazine; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D019808:Losartan; D009638:Norepinephrine