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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Research Outline


Research related to molecular mechanisms of blood pressure regulation and sympathetic nerve control by circulating biologically active substances and their pathophysiological significance




Many mechanisms for the control of circulatory dynamics have been elucidated. Needless to say, the sympathetic nervous system plays a major role in the regulation of circulatory dynamics. Especially, the sympathetic nervous system is implicated to be intrinsically related to the pathophysiology of hypertension and heart failure, but the mechanisms involved remain unknown. Many circulating biologically active substances are associated with the control of circulation, and they maintain normal circulation through intricate modification of the sympathetic nervous system. In contrast, abnormalities of these substances are suggested to cause over-reactivity of the sympathetic nervous system, thereby resulting in a viscous cycle of cardiovascular pathophysiology. Although numerous studies have been devoted to the renin-angiotensin system, which plays a key role as humoral factors, research related to its control by the sympathetic nervous system is rare despite its importance. Hypertension is the most common risk factor of cardiovascular diseases and also a very common underlying condition of heart failure. Having already reached a super-aging society in Japan, the importance of controlling and treating hypertension continues to increase. Hypertension, a symptom of the metabolic syndrome that has attracted attention in recent years, is also closely associated with the activity of the sympathetic nervous system. In our unit, we have pursued our research based on the philosophy that if we can elucidate the molecular mechanisms of blood pressure regulation and sympathetic nerve control by circulating biologically active substances under disease conditions, it will advance our understanding of the pathophysiology of the diseases, paving a way for the development of novel diagnostic and therapeutic strategies based on the mechanisms.


The results of our basic and clinical research suggest that nitric oxide (NO), reactive oxygen species, and Rho-kinase, which have been extensively studied as circulating biologically active substances, are closely related to the over-reactive sympathetic nervous and abnormal peripheral circulation in patients with hypertension and heart failure. We have also demonstrated that these abnormalities occur not only in peripheral blood vessels but also in the cerebral cardiovascular center; consequently they have great impact on the systemic circulatory dynamics. In addition, our studies also showed that an imbalance of these substances leads to over-reactivity of sympathetic nerves and that angiotensin receptor blocker and statin may correct these abnormalities. In the future, by elucidating the molecular mechanisms of how these factors modify the sympathetic nervous activity in hypertension and heart failure, we wish to develop novel therapies by targeting these mechanisms, the success of which will contribute to the health of the super-aging society.


  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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