title: HO-1 induction improves the type-1 cardiorenal syndrome in mice with impaired angiotensin II-induced lymphocyte activation.
abstract: Type-1 cardiorenal syndrome, characterized by acute kidney dysfunction secondary to cardiac failure and renal arteriolar vasoconstriction, is mediated by the renin-angiotensin-aldosterone axis and sympathetic nervous system activation. Previous reports indicate that angiotensin II modulates immune function and causes recruitment and activation of T-lymphocytes. The goal of this study was to evaluate the effects of postischemic heart failure on renal morphology and circulation and the beneficial effects of heme oxygenase-1 (HO-1) induction in T-lymphocyte-suppressed severe combined immune deficiency (SCID) mice. Mice were divided into 4 groups: sham, myocardial infarction (MI), MI treated with an HO-1 inducer, cobalt protoporphyrin, and with or without stannous mesoporphyrin, an inhibitor of HO activity. Heart and kidney function were studied 30 days after surgery. Fractional area change was reduced 30 days after surgery in both the C57 and SCID MI-groups as compared with their respective controls (P<0.01). Renal Pulsatility Index and renal injury were increased in C57 and SCID MI-groups compared with the sham group. HO-1 induction improved renal vasoconstriction as well as ameliorated renal injury in both the SCID and C57 MI-groups (P<0.01). However, improvement was more evident in SCID mice. In addition, our results showed that plasma creatinine, angiotensin II, and renin were significantly increased in the C57 and SCID MI-groups as compared with their respective controls. HO-1 induction decreased these parameters in both MI groups. Stannous mesoporphyrin reversed the beneficial effect of cobalt protoporphyrin in both mouse strains. The study demonstrates that T-lymphocyte suppression facilitated the HO-1-dependent improvement in the attenuation of type-1 cardiorenal syndrome.
authors.affiliation: Department of Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701-3655, USA.
authors.forename: Sumit R
authors.initials: SR
authors.lastname: Monu
authors.forename: Paola
authors.initials: P
authors.lastname: Pesce
authors.forename: Komal
authors.initials: K
authors.lastname: Sodhi
authors.forename: Massimo
authors.initials: M
authors.lastname: Boldrin
authors.forename: Nitin
authors.initials: N
authors.lastname: Puri
authors.forename: Larisa
authors.initials: L
authors.lastname: Fedorova
authors.forename: David
authors.initials: D
authors.lastname: Sacerdoti
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Peterson
authors.forename: Nader G
authors.initials: NG
authors.lastname: Abraham
authors.forename: Attallah
authors.initials: A
authors.lastname: Kappas
mesh_terms: D000804:Angiotensin II / Q000097:blood / Q000502:physiology*; D000818:Animals; D001835:Body Weight; D059347:Cardio-Renal Syndrome / Q000201:enzymology / Q000276:immunology*; D003404:Creatinine / Q000097:blood; D004452:Echocardiography; D004790:Enzyme Induction; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D007668:Kidney / Q000000981:diagnostic imaging / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D012083:Renin / Q000097:blood
chemical_list: D000804:Angiotensin II; D003404:Creatinine; D051547:Heme Oxygenase-1; D012083:Renin
keywords: T-lymphocytes; angiotensin II; heart failure; heme oxygenase-1; vasoconstriction