Altered Responsiveness to Humoral Factors in Cardiac Myocytes of Cardiomyopathic Syrian Hamsters

Abstract

It has been considered that neurohumoral factors, such as catecholamines and renin angiotensin system, may play an important role in the development of cardiomyopathy [1–4]. Previous studies have demonstrated that α-adrenergic stimulation and angiotensin II (Ang II) receptor stimulation result in increased protein synthesis and cell hypertrophy [5–7]. In addition, α-adrenergic stimulation reportedly causes intracellular Ca2+ overload in myocytes of cardiomyopathic hamsters [8]. On the other hand, these neurohumoral factors may also play a role in the maintenance of cardiac performance in failing heart, in which β-adrenoceptor-mediated positive inotropic response is compromised [9–11]. α-Adrenergic stimulation and Ang II receptor stimulation are reported to produce positive inotropic responses in human failing myocardium [12,13]. The Syrian hamster of genetic cardiomyopathy is a widely utilized model of congestive cardiomyopathy [14]. Since BIO 14.6 strain develops hypertrophy at 85–150 days of age before the appearance of overt congestive ljeart failure [14], it has been used as a model of hypertrophic cardiomyopathy. In contrast, BIO 53.58 develops a dilated cardiomyopathy, which is characterized by thin ventricular walls and dilated chambers, throughout most of its life, and is used as a model of the idiopathic congestive cardiomyopathy [15]. In the present study we evaluated electromechanical responses to α-adrenoceptor and Ang II receptor stimulation in these two models of cardiomyopathy using conventional microelectrode techniques. In addition, we evaluated the ionic mechanisms underlying the difference of the electromechanical responses in isolated ventricular myocytes of the hamsters using patch clamp techniques.