2003 Fiscal Year Final Research Report Summary
Study on the role of the kallikrein-kinin system in the cardiovascular diseases
| Project/Area Number |
13672315
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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 |
Biological pharmacy
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| Research Institution | Kobe Gakuin University |
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Principal Investigator |
OKAMOTO Hiroshi Kobe Gakuin University, Faculty of Pharmaceutical Science, Department of Pharmacology, Professor, 薬学部, 教授 (00028870)
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| Co-Investigator(Kenkyū-buntansha) |
TAKANO Masaoki Kobe Gakuin University, Faculty of Pharmaceutical Science, Department of Pharmacology, Assistant Professor, 薬学部, 助手 (30258107)
YAYAMA Katsutoshi Kobe Gakuin University, Faculty of Pharmaceutical Science, Department of Pharmacology, Associate Professor, 薬学部, 助手 (30248108)
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| Project Period (FY) |
2001 – 2003
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| Keywords | heart / bradykinin / angiotensin / B2-receptor / angiotensin receptor / cardiac hypertrophy / hypertension / vessel |
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| Research Abstract |
Studies have been undertaken to elucidate a role of the kallikrein-kinin system(KKS) in the cardiovascular diseases, such as the cardiac hypertrophy and hypertension. The abdominal aortic banding produced a transient reduction of the bradykinin B2-receptor mRNA in mouse heart before a development of the cardiac hypertrophy. The administration of angiotensin II(Ang II) type 1(AT1) receptor antagonist inhibited the pressure-overload-induced down-regulation of cardiac B2-receptor, suggesting a role of the renin-angiotensin system in regulating B2-receptor expression in cardiac tissue. Tisssue kallikrein was found to be synthesized and secreted by human endothelial cells, suggesting a presence of the local KKS,in vascular endothelium. The abdominal aortic banding produced an up-regulation of the Ang II type 2(AT2) receptor mRNA in pressure-overloaded thoracic aorta in rats and mice, and the administration of AT1-receptor antagonist inhibited the up-regulation of aortic AT2-receptor. The contractile response to Ang II was decreased in pressure-overloaded thoracic aorta in the endothelium-dependent manner, and the decreased response restored to sham-levels by either. AT2-receptor antagonist or B2-receptor antagonist. The aortic banding elicited a marked increase in cGMP content of pressure-overloaded thoracic aortas, and the administration of antagonists for either AT2-or B2-receptor reduced the elevated cGMP contents to sham levels. These results suggest that the aortic banding induced down-regulation of cardiac B2-receptor expression via the activation of AT1-receptor, while the up-regulation of the AT2-receptor in pressure-overloaded aorta through increased circulating Ang II via the AT1-receptor, thereby activating a vasodilatory pathway in vessels through the AT2-receptor via the kinin/cGMP system.
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