Studies on the developmental and species difference of cardiac function : analysis of pharmacological and physiological specificity of mouse myocardia

心脏功能的发育和物种差异的研究：小鼠心肌的药理和生理特异性分析

• 批准号: 11670106
• 负责人: KOKI Shigenobu
• 金额: $ 2.24万
• 依托单位: TOHO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670106/
• 关键词: mouse myocardium; alpha-adrenergic effect; endothelin; angiotensin I; endocardial endothelium; prostaglandin; action potential; Na+, Ca2+ exchange

Research results are summarized as follows.1) Mechanisms underlying the negative inotropic response to alpha-adrenergic stimulation in adult mouse ventricular myocardium were studied. Results obtained in the present study suggest that the sutained negative inotropic response to alpha-adrenoceptor stimulation of adult mouse ventricular myocardium is mediated by enhancement of Ca2+ efflux through the Na+/Ca2+ exchanger.2) Alpha-adrenergic stimulation results in a negative inotropic response in adult mouse myocardia as described above, while it produces positive inotropism in neonatal myocardia. Similar developmental conversion of inotropism was observed with endothelin I and angiotensin II ; these agents produced positive response in the neonate but negative in the adult.3) In mouse left atria, acetylcholine produced a biphasic inotropic response, i.e., a transient decrease in contractile force followed by a late increase. The positive response was found to be mediated by prostaglandin released from the endocardial endothelium.

主要研究结果如下：1）研究了成年小鼠心室肌对α-肾上腺素能刺激的负性变力反应的机制。结果提示：（1）α-肾上腺素能受体刺激成年小鼠心室肌可引起持续的负性变力反应，其机制可能是通过增加Na+/Ca ~（2+）交换器的Ca ~（2+）流出而实现的。（2）α-肾上腺素能受体刺激成年小鼠心肌可引起上述负性变力反应，而对新生小鼠心肌可产生正性变力反应。内皮素I和血管紧张素II也观察到类似的变力性发育转变;这些药物在新生儿中产生阳性反应，但在成人中呈阴性。3）在小鼠左心房中，乙酰胆碱产生双相变力性反应，即，收缩力的短暂下降，随后是后期的增加。发现阳性反应是由内皮细胞释放的前列腺素介导的。

项目成果

Nishimaru,K.,-,Shigenobu,K.: "Alpha-adrenoceptor mediated negative inotropism and enhancement of Na+,Ca2+ exchange in mouse ventricle"American Journal of Physiology. 280. H132-H141 (2001)

Nishimaru,K.,-,Shigenobu,K.：“α-肾上腺素受体介导的负性肌力作用和小鼠心室 Na 、Ca2 交换的增强”美国生理学杂志。

Tanaka,H.…,Shigenobu,K.: "Acetylcholine-induced positive inotropy mediated by prostaglandin released from endocardial endothelium in mouse left atrium."Naunyn-Schmiedeberg's Arch.Pharmacol.. (in press). (2001)

Tanaka, H.…, Shigenobu, K.：“由小鼠左心房心内膜内皮释放的前列腺素介导的乙酰胆碱诱导的正性肌力。”Naunyn-Schmiedeberg 的 Arch.Pharmacol..（出版中）。

Tanaka,H.,-,Shigenobu,K.: "Acetylcholine-induced positive inotropism mediated by prostaglandin released from endocardial endothelim in mouse left atrium"Naunyn-Schmiedeberg's Arch.Pharmacol.. (in press). (2001)

Tanaka, H.,-, Shigenobu, K.：“由小鼠左心房心内膜内皮释放的前列腺素介导的乙酰胆碱诱导的正性肌力作用”Naunyn-Schmiedeberg 的 Arch.Pharmacol..（出版中）。

Nishimaru,K.,….…,Shigenobu,K.: "Positive and negative inotropic effects of muscarinic receptor stimulation in mouse left atria"Life Sciences. 66. 607-615 (2000)

Nishimaru, K.,….…, Shigenobu, K.：“小鼠左心房毒蕈碱受体刺激的正性和负性肌力作用”生命科学 66. 607-615 (2000)。

Nishimaru K., Makuta R., Tanaka Y, Tanaka H., Shigenobu K.: "Pharmacological properties of excitation-contraction mechanisms in isolated mouse left atria."Pharmacology. 62. 87-91 (2001)

Nishimaru K.、Makuta R.、Tanaka Y、Tanaka H.、Shigenobu K.：“离体小鼠左心房兴奋收缩机制的药理学特性。”药理学。