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.

本研究旨在研究咪唑啉受体对狗血小板和心血管系统的药理学特征。此外，还确定了美国可卡犬的遗传性扩张型心肌病，以及咪唑啉受体药物对扩张型心肌病的作用。对心肌病狗进行了检查，结果表明有两种亚型的非肾上腺素I受体，I_1和I_2，以及此外，本研究表明，犬血小板上存在α_<2A>-肾上腺素受体亚型，I_1亚型与GTP结合蛋白偶联，而I_2作为咪唑啉受体作用剂抑制肾上腺素增强的血小板聚集。狗，并诱导血管扩张，咪唑啉受体剂可能有助于治疗血栓形成和心血管疾病。这项研究揭示了这一过程和。扩张型心肌病狗的病理生理学此外，犬扩张型心肌病的α_2-肾上腺素受体和咪唑啉受体结合以及血浆儿茶酚胺测量结果表明，观察到血小板上α_2-肾上腺素受体数量减少和血浆肾上腺素浓度增加呈显着负相关。然而，血小板上I_1-和I_2-受体数量的减少与血浆之间的相关性因此，这些结果表明，与α_2-肾上腺素能药物相比，I_1-和I_2-受体作用药物可能更有助于治疗狗的心血管疾病。可能需要进一步研究来研究I_1的功能。和 I_2 受体在犬心肌病中的作用。

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

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》。

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。