[Electromechanical responsiveness to alpha 1-adrenoceptor and angiotensin II receptor stimulation in the ventricular myocardium of hypertrophied and dilated cardiomyopathic Syrian hamsters]

Abstract

It has been postulated that neurohumoral factors, such as sympathetic nervous system or renin-angiotensin system, may play an important role in the development of myocardial lesion in cardiomyopathic hamsters. This study was undertaken to determine whether the electromechanical responsiveness of the ventricular myocardium to alpha 1-adrenoceptor and angiotensin II (Ang II) receptor stimulation is altered in cardiomyopathic (CM) Syrian hamsters. Changes of action potential and isometric tension in response to these receptors stimulation were examined in left ventricular papillary muscles of 14-20 week-old normal (F1 beta), hypertrophic (BIO 14.6) and dilated (BIO 53.58) cardiomyopathic hamsters using conventional microelectrode techniques. Action potential duration (APD) recorded from the papillary muscles (PMs) of BIO 14.6 was significantly shorter than that recorded from BIO 53.58 and F1 beta PMs. Developed tension, which was corrected for the cross-sectional area of PMs, was significantly reduced in PMs of both cardiomyopathic hamsters than those of normal hamsters. Phenylephrine (0.3-30 microM) in the presence of propranolol (1 microM) produced concentration-dependent increases in APD and DT in PMs of normal and cardiomyopathic hamsters. Increases in APD and DT in response to 30 microM phenylephrine (PHE) in BIO 14.6 PMs were significantly greater than those in PMs of F1 beta. However, the increases in APD and DT produced by alpha 1-adrenergic stimulation in BIO 53.58 PMs were comparable to those observed in F1 beta PMs. In order to define ionic mechanism(s) responsible for the greater increase in APD during alpha 1-adrenergic stimulation in PMs of BIO 14.6, effects of PHE on membrane currents were examined in ventricular cells of F1 beta and BIO 14.6 using patch clamp techniques. PHE-induced decrease in the transient outward current (I(to)) in BIO 14.6 cells was similar to that in F1 beta cells. However, PHE produced a significantly greater decrease in the inward rectifier potassium current (IK1) in BIO 14.6 myocytes than in F1 beta ones. The greater inhibition of IK1 may, at least in part, explain the greater prolongation of APD in BIO 14.6 PMs. Angiotensin II (Ang II, 0.01-1 microM) also produced concentration-dependent increases in APD and DT in PMs of normal and cardiomyopathic hamsters. In contrast to electromechanical responses to alpha 1-adrenergic stimulation, Ang II produced a significantly smaller increase in DT in BIO 14.6 PMs than F1 beta ones, concomitantly with a smaller increase in APD. The Ang II-induced increase in DT in BIO 53.58 PMs was also smaller than that in F1 beta PMs.(ABSTRACT TRUNCATED AT 400 WORDS)