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

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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.