Establishment of genetically dilated cardiomyopathy and usefulness of imidazoline receptor-acting agents in dogs

遗传性扩张型心肌病的建立以及咪唑啉受体作用剂在犬中的用途

• 批准号: 14560266
• 负责人: HIKASA Yoshiaki
• 金额: $ 1.86万
• 依托单位: National University Corporation Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14560266/
• 关键词: Dog; Platelet; Dilated cardimyopathy; Imidazoline receptor; Cardiovascular system; Genetics; Adrenoceptor; Catecholamine; カルニチン; タウリン; 心筋症

The present study was conducted to investigate the pharmacological characteristics of imidazoline receptors on platelets and cardiovascular systems in dogs. In addition, the genetically dilated cardiomyopathy in the dog, American cocker spaniel, was established, and the usefulness of imidazoline receptor acting agents for the dilated caridiomyopathy dog was examined. The results demonstrated that two subtypes of non-adrenergic I receptors, I_1 and I_2, as well as the α_<2A>-adrenoceptor subtype exists on canine platelets. In addition, this study suggested that I_1 subtype was coupled with GTP-binding proteins, and I_2 was not coupled with those. As imidazoline receptor acting agents inhibit the adrenaline-potentiated platelet aggregation in dogs, and induce vascular dilatation, imidazoline receptor agents may be useful for the treatment of thrombosis and caridiovascular diseases. This study revealed the process and pathophysiology of the dilated caridiomyopathy dog. Furthermore, the results of α_2-adrenoceptor and imidazoline receptor binding and the plasma catecholamine measurements in canine dilated caridiomyopathy revealed that significant negative correlations were observed for reduced number of α_2-adrenoceptors on platelets, and increased plasma adrenaline concentrations. However, the correlation between the reduced number of I_1- and I_2-receptors on platelets and the plasma catecholamine concentrations was not significant. Therefore, these results indicated that I_1- and I_2-receptor acting agents compared with α_2-adrenergic agents may be more useful for the treatment of cardiovascular disease in dogs. Further studies may be required to investigate the function of I_1 and I_2 receptors in canine cardiomyopathy.

本研究旨在探讨咪唑啉受体在犬血小板和心血管系统上的药理学特性。此外，还建立了美国可卡犬的遗传扩张型心肌病模型，并检测了咪唑啉受体激动剂对扩张型心肌病犬的有效性。结果表明，犬血小板上存在I_1和I_2两种非肾上腺素能受体亚型，以及α_1和I2-受体亚型。此外，本研究还表明，I_1亚型与GTP结合蛋白偶联，而I_2亚型与GTP结合蛋白不偶联。由于咪唑啉受体激动剂抑制肾上腺素增强的犬血小板聚集，并诱导血管扩张，咪唑啉受体激动剂可能用于血栓形成和心血管疾病的治疗。本研究揭示了扩张型心肌病犬的发病过程和病理生理过程。此外，犬扩张型心肌病的α_2受体和咪唑啉受体结合及血浆儿茶酚胺的测定结果表明，血小板上α_2受体数量的减少和血浆肾上腺素浓度的升高呈显著负相关。而血小板I_1、I_2受体数量减少与血浆儿茶酚胺浓度的相关性不显著。这些结果表明，与α_2受体激动剂相比，I_1和I_2受体激动剂可能更适用于犬心血管疾病的治疗。I_1和I_2受体在犬心肌病中的作用有待进一步研究。

项目成果

Quantitative electroencephalography of medetomidine, medetomidine-midazolam and medetomidine-midazolam-butorphanol in dogs

犬美托咪定、美托咪定-咪达唑仑和美托咪定-咪达唑仑-布托啡诺的定量脑电图

• 发表时间: 2002
• 期刊: Journal of Veterinary Medicine, Series A 49・4
• 作者: Tamas Ambrisko;T.D.Ambrisko;K.Tsujino;Tamas Ambrisko;Tamas Ambrisko;Tamas Ambrisko;Yoshiaki Hikasa;Kazuhito Itamoto
• 通讯作者: Kazuhito Itamoto

Influence of medetomidine on stress-related neurohormonal and metabolic effects caused by butorphanol, fentanyl and ketamine in dogs

美托咪定对布托啡诺、芬太尼和氯胺酮引起的犬应激相关神经激素和代谢影响的影响

• 发表时间: 2005
• 期刊: American Journal of Veterinary Research 66・3
• 作者: Tamas Ambrisko

Chronic Myocardial Infarction Due to Arteriosclerosis of Coronary Arteries Followed by Acute Thromboembolism of Caudal Abdominal Aorta in a Cat

猫冠状动脉硬化继发尾部腹主动脉急性血栓栓塞所致慢性心肌梗塞

• 发表时间: 2005
• 期刊: Journal of Veterinary Medical Sciences 67(In press)
• 作者: Tamas Ambrisko;T.D.Ambrisko;K.Tsujino
• 通讯作者: K.Tsujino

Yoshiaki Hikasa: "Cardiopulmonary hematological serum biochemcal and behavioural effects of sevoflurane compared with isoflurane or haolthane in spontaneously ventilating goats"Small Ruminant Research. 43. 167-178 (2002)

Yoshiaki Hikasa：“与异氟烷或浩烷相比，七氟烷对自发通气山羊的心肺血液学血清生化和行为影响”小反刍动物研究。

Tamas Ambrisko: "The antagonistic effects of atipamezole and yohimbine on stress-related neurohormonal and metabolic responses induced by medetomidine in dogs"Canadian Journal of Veterinary Research. 67. 64-67 (2002)

Tamas Ambrisko：“阿替美唑和育亨宾对美托咪定诱导的狗应激相关神经激素和代谢反应的拮抗作用”《加拿大兽医研究杂志》。