DEPRESSED RESPONSIVENESS TO ANGIOTENSIN-II IN VENTRICULAR MYOCYTES OFHYPERTROPHIC CARDIOMYOPATHIC SYRIAN-HAMSTER

Electromechanical responsiveness to angiotensin II (Ang II) receptor s timulation in ventricular myocardium and myocytes of hypertrophic card iomyopathic Syrian hamsters (BIO 14.6) was examined and compared with that in preparations of normal hamsters (F1B) using conventional micro eIectrode and patch clamp techniques. Action potential duration (APD) and developed tension (DT) corrected for the cross-sectional area of t he papillary muscles of 14-20 week-old BIO 14.6 hamsters were signific antly smaller than those in preparations of age-matched normal hamster s. An Ang II (1 mu M)-induced increase in DT in BIO 14.6 papillary mus cles (24.7 +/- 11.0%) was significantly smaller than that in F1B papil lary muscles (53.8 +/- 8.5%), which was associated with a smaller incr ease in APD in BIO 14.6 papillary muscles. In ventricular myocytes of both BIO 14.6 and F1B hamsters, Ang II increased the calcium current ( I-Ca) following a transient decrease in I-Ca. However, the magnitude o f the Ang II-induced increase in I-Ca in BIO 14.6 myocytes (35.5 +/- 7 .5%) was significantly smaller than that in F1B myocytes (86.0 +/- 19. 7%), suggesting a causal relationship between I, and mechanical respon se to Ang II in these hamsters. The depressed responsiveness to Ang II receptor stimulation in hypertrophic cardiomyopathic hamster is in a marked contrast with the enhanced responsiveness to alpha(1)-adrenergi c stimulation, which was demonstrated by previous studies, and may be one of adaptational changes to the activated renin-angiotensin system in the cardiomyopathy.