DEPARTMENT OF CARDIOVASCULAR MEDICINE KYUSHU UNIVERSITY GRADUATE SCHOOL OF MEDICAL SCIENCES

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Research Units

Hypertension & Autonomic Nervous Function Research Unit


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menu Research Outline Main Research Themes and Relevant Publications Principle Investigator of the group Staff and Research Focus Research Outline Main Research Themes and Relevant Publications Profile of Lead Researcher Staffs and the Research Focus 研究概要 主要なテーマと関連論文 主任研究者情報 研究室情報

Main Research Themes and Relevant Publications


  1. Basic research on blood pressure regulation and sympathetic nerve control by circulating biologically active substances: to elucidate the intracerebral target molecular mechanisms for the activation of sympathetic nervous activity in hypertension and heart failure by gene transfer into the cardiovascular center
  2. To develop clinical research related to the effects of circulating biologically active substances on peripheral and coronary abnormalities and elucidate its pathophysiological significance

2. Clinical Research: To develop clinical research related to the effects of circulating biologically active substances on peripheral and coronary abnormalities and elucidate its pathophysiological significance




The method of evaluating endothelial function using acetylcholine which we developed is now the gold standard worldwide. Using this method, we were the first in the world to demonstrate the importance of endothelial function abnormality in cardiovascular diseases, and paved the way for subsequent research on the pathogenesis. Especially, our results showing the improvement of endothelial function by angiotensin converting enzyme inhibitor (Hirooka Y, et al. Hypertension 1992) and statin (Masumoto A, Hirooka Y, et al. Am J Cardiol 2001) and our data showing the roles of NO in heart failure patients with abnormal peripheral circulation (Hirooka Y, et al. Circulation 1994) are highly significant because they are the first scientific evidence to suggest the pleiotropic effects of these drugs. These reports formed the basis for advocating the concept in recent years that improvement of endothelial function is a barometer of cardiovascular therapies.

Our recent research findings have elucidated a strong association of the activation of Rho-kinase with peripheral circulation abnormality in patients with hypertension or heart failure (Masumoto A, Hirooka Y, et al. Hypertension 2001, Kishi T, Hirooka Y, et al. Circulation 2005). The research results of Matsumoto et al. suggest a strong association between Rho-kinase activation and increased peripheral vascular resistance also in humans, and their work has been cited by many investigators. The article of Kishi et al., which reported for the first time the role of Rho-kinase in peripheral circulation of patients with heart failure, was discussed in the Issue Highlights of Circulation, and Kishi received the CPIS award from the Japanese Circulation Society. The above achievements provide evidence that Rho-kinase activation plays an important role in peripheral circulation abnormality associated with hypertension and heart failure, which may suggest a new therapeutic possibility of targeting Rho-kinase that exists downstream of neurohumoral factors activated as a result of hypertension and heart failure.

Relevant publications
  1. Kishi T, Hirooka Y, Masumoto A, Ito K, Kimura Y, Inokuchi K, Tagawa T, Shimokawa H, Takashita A, Sunagawa K. Rho-kinase inhibitor improves increased vascular resistance and impaired vasodilation of the forearm in patients with heart failure. Circulation. 111: 2741-2747, 2005.
  2. Inokuchi K, Hirooka Y, Shimokawa H, Sakai K, Kishi T, Ito K, Kimura Y, Takeshita A. Role of endothelium-derived hyperpolarizing factor in human forearm circulation. Hypertension. 42: 919-924, 2003.
  3. Hirooka Y, Eshima K, Setoguchi S, Kishi T, Egashira K, Takeshita A. Vitamin C improves a attenuated angiotensin II-induced endothelium-dependent vasodilation in human forearm vessels. Hypertens Res. 26: 953-959, 2003.
  4. Setoguchi S, Hirooka Y, Eshima K, Shimokawa H, Takeshita A. Tetrahydrobiopterin improves the impaired endothelium-dependent forearm vasodilation in patients with heart failure. J Cardiovasc Pharmacol. 39: 363-368, 2002.
  5. Tagawa T, Hirooka Y, Shimokawa H, Hironaga K, Sakai K, Oyama J-I, Takeshita A. Long-term treatment with eicosapentaenoic acid improves exercised-induced vasodilation in patients with coronary artery disease. Hypertens Res. 25: 823-829, 2002.
  6. Masumoto A, Hirooka Y, Hironaga K, Eshima K, Setoguchi S, Egashira K, Takeshita A. Effect of pravastatin on endothelial function in patients with coronary artery disease. Am J Cardiol. 88: 1291-1294, 2001.
  7. Masumoto A, Hirooka Y, Shimokawa H, Hironaga K, Setoguchi S, Takeshita A. Possible involvement of Rho-kinase in the pathogenesis of hypertension in humans. Hypertension. 38: 1307-1310, 2001.

  1. Basic research on blood pressure regulation and sympathetic nerve control by circulating biologically active substances: to elucidate the intracerebral target molecular mechanisms for the activation of sympathetic nervous activity in hypertension and heart failure by gene transfer into the cardiovascular center
  2. To develop clinical research related to the effects of circulating biologically active substances on peripheral and coronary abnormalities and elucidate its pathophysiological significance

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