Depressed responsiveness to angiotensin II in ventricular myocytes of hypertrophic cardiomyopathic Syrian hamster.
Electromechanical responsiveness to angiotensin II (Ang II) receptor stimulation in ventricular myocardium and myocytes of hypertrophic cardiomyopathic Syrian hamsters (BIO 14.6) was examined and compared with that in preparations of normal hamsters (F1B) using conventional microelectrode and patch clamp techniques. Action potential duration (APD) and developed tension (DT) corrected for the cross-sectional area of the papillary muscles of 14-20 week-old BIO 14.6 hamsters were significantly smaller than those in preparations of age-matched normal hamsters. An Ang II (1 microM)-induced increase in DT in BIO 14.6 papillary muscles (24.7 +/- 11.0%) was significantly smaller than that in F1B papillary muscles (53.8 +/- 8.5%), which was associated with a smaller increase 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 (ICa) following a transient decrease in ICa. However, the magnitude of the Ang II-induced increase in ICa 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 ICa and mechanical response 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-adrenergic stimulation, which was demonstrated by previous studies, and may be one of adaptational changes to the activated renin-angiotensin system in the cardiomyopathy.
Yamashita
T
T
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Nakaya
H
H
Tohse
N
N
Kusaka
M
M
Uemura
H
H
Sakuma
I
I
Yasuda
H
H
Kanno
M
M
Kitabatake
A
A
D000200:Action Potentials / Q000187:drug effects; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002312:Cardiomyopathy, Hypertrophic / Q000188:drug therapy* / Q000503:physiopathology; D006224:Cricetinae; D006352:Heart Ventricles / Q000187:drug effects; D008647:Mesocricetus; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D002118:Calcium