2005 Fiscal Year Final Research Report Summary
Role of intracellular signal transmission and its application to treatment in hypertensive heart failure.
| Project/Area Number |
16590712
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Dokkyo Medical University |
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Principal Investigator |
MATSUOKA Hiroaki Dokkyo Medical University, School of Medicine, Professor, 医学部, 教授 (20111544)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Naohiko Dokkyo Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (90254945)
ISHIMITSU Toshihiko Dokkyo Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (80232346)
NISHIKIMI Toshio Dokkyo Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (80291946)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Dahl salt sensitive rat / hypertensive cardiac hypertrophy / heart failure / betaxolol / quinapril / eplerenone / oxidative stress / eNOS |
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| Research Abstract |
To elucidate a role of intracellular signal transmission in hypertensive heart disease is important to understand pathological conditions of heart failure and to apply to treatment.
1)Cardioprotective effects of betaxolol (a β blocker) and quinapril (an ACE inhibitor) on intracellular signal transmission in Dahl salt sensitive hypertensive rats (Dahl rats ; hypertrophy stage) were examined. Cardiac function and remodeling were improved by these agents and cardioprotective effects of these agents may be mediated by increased expression of eNOS and suppressed expression of LOX-1. Eplerenone (a selective aldosterone antagonist) improved renal glomerular sclerosis index in Dahl rats (hypertrophy stage) by inhibiting pathways of PKC-MAPK-p90RSK and Rho-kinase.
2)In Dahl salt sensitive hypertensive heart failure rats, FR167653 (a p38MAPK inhibitor) ameliorated renal damage as well as inhibited renal expression of Il-1β and TNF-α. Thus, cytokines' expression induced by a MAPK pathway may be involved in renal damage in hypertensive heart failure. Eplerenone improved cardiac function and remodeling in hypertensive heart failure and these cardioprotective effects of eplerenone may be mediated by increased expression of eNOS induced by a Akt/PKB pathway, suppressed iNOS induced by a oxidative stress and NF-κB pathway, and inhibition of a PKC/Src/EPK/p70S6K pathway.
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[Journal Article] Eplerenone shows renoprotective effect by reducing LOX-1-mediated adhesion molecule, PKC ε MAPK-p90RSK, and Rho-kinase pathway.2005
Author(s)
Kobayashi N, Hara K, Tojo A, Onozato ML, Honda T, Yoshida K, Mita SI, Nakano S, Tsubokou Y, Matsuoka H
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Journal Title
Hypertension 45
Pages: 538-544
Description
「研究成果報告書概要(欧文)」より
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