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Relation between cardiovascular diseases and cardiac hormones

心血管疾病与心脏激素的关系

基本信息

批准号：
17390233
负责人：
YOSHIMURA Michihiro
金额：
$ 9.28万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390233/
关键词：
aldosterone cardiac hypertrophy dehydration natriuretic peptide natrium channel sodium oxidative stress rennin-angiotensin system 心不全高血圧腎不全 RAA系抑制薬カリウム hANP BNP ACTH アンジオテンシンII HPA軸

项目摘要

The heart is a pump organ; however, it might produce many hormones in heart failure. Especially ANP and BNP are synthesized in large quantities. We have recently shown that various kinds of steroid hormone are also synthesized with a very small quantity. On the other hand, the action of steroid hormones in the heart may also exceed the conventional concept. In this study, we found that aldosterone has an action for anti-cellular dehydration; Na^+/H^+ exchanger 1 (NHE1) plays an important role there deeply. Cell shrinkage under high osmolarity was prevented by making Na^+ flow into the cell. However, when this became a long period, the rise of intracellular Ca^<2+> concentration leaded to cardiac hypertrophy.From the clinical side, we advanced researches on the medical treatment of heart failure. Although the inhibitory drugs of the renin-angiotensin system and anti-aldosterone agents are indispensable, too much rise of the potassium concentration is an important problem. We examined in detail what kind of factors would influence the potassium concentration by using 1,035 patients admitted to our institution. As a result, although renal insufficiency, diabetes, and use of the inhibitory drugs of the RAA system raised the potassium concentration, it was reduced rather in heart failure status. This is contrary to the conventional research findings; and thus the further argument is needed. On the other hand, although hANP is used more often in acute heart failure, there are still unknown mechanisms. In this study, we divided the heart failure patients into two groups; hANP treatment group and furosemide treatment group. Although the improvement of hemodynamic parameters were almost similar, the improvement of oxidative stress was significantly lager in the hANP group. This action will be confirmed also in the experiment using cultured neonatal rat cardiomyocyte, and the elucidation of that mechanism is a future subject.

心脏是一个泵器官；然而，它可能会产生许多导致心力衰竭的激素。尤其是ANP和BNP的合成量很大。我们最近发现，各种类固醇激素也可以以极少量的量合成。另一方面，类固醇激素在心脏中的作用也可能超出常规概念。在这项研究中，我们发现醛固酮具有抗细胞脱水的作用； Na^+/H^+ 交换器 1 (NHE1) 在那里发挥着重要作用。通过使 Na^+ 流入细胞来防止高渗透压下的细胞收缩。但时间长了，细胞内Ca^2+浓度升高，导致心脏肥大。从临床方面，我们对心力衰竭的药物治疗进行了深入的研究。虽然肾素-血管紧张素系统的抑制药物和抗醛固酮药物是不可缺少的，但钾浓度升高过多是一个重要问题。我们通过使用本机构收治的 1,035 名患者详细研究了哪些因素会影响钾浓度。结果，虽然肾功能不全、糖尿病和使用RAA系统抑制药物使钾浓度升高，但在心力衰竭状态下钾浓度反而降低。这与传统的研究结果相反；因此需要进一步论证。另一方面，虽然hANP更常用于急性心力衰竭，但仍存在未知的机制。在这项研究中，我们将心力衰竭患者分为两组； hANP治疗组和呋塞米治疗组。虽然血流动力学参数的改善几乎相似，但 hANP 组氧化应激的改善明显更大。该作用也将在使用培养的新生大鼠心肌细胞的实验中得到证实，并且该机制的阐明是未来的课题。