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 b iliverdin, iron, and carbon monoxide. HO-1, an inducible form of HO, is tho ught to act as an endogenous antioxidant defense mechanism. To determine wh ether chronic administration of angiotensin II affects HO-1 expression in t he heart, expression and localization of HO-1 were investigated in the hear t 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 gra nulation tissue, characterized by myofibroblast proliferation, fibrous depo sition, and inflammatory cell migration. Angiotensin II also upregulated ca rdiac HO-1 expression. Immunohistochemistry revealed that HO-1 was intensiv ely expressed in the granulation tissue. The selective AT(1)-receptor antag onist, losartan, completely, but hydralazine only partially, suppressed ang iotensin II-induced granulation tissue formation and HO-1 upregulation. Chr onic norepinephrine infusion (2.8 mg . kg(-1) . day(-1)) did not induce gra nulation tissue formation or HO-1 upregulation. Our data suggest that angio tensin II upregulates cardiac HO-1 expression in the newly formed inflammat ory lesion, which may represent an adaptive response to angiotensin II-indu ced cardiac damage.