Angiotensin II-induced apoptosis in cultured adult rat ventricular myocytes.
Angiotensin II (Ang II)-induced apoptosis was demonstrated for the first time in cultured adult rat ventricular myocytes (ARVMs) isolated by retrograde heart perfusion with Krebs-Henseleit bicarbonate (KHB) buffer containing collagenase and hyaluronidase. ARVMs incubated with 10 mumol/L Ang II for 48 h showed morphological features of apoptosis (cellular shrinkage, condensation of cytoplasm) and a characteristic "ladder" of DNA bands representing integer multiples of the internucleosomal DNA length about 180-200 bp, which became more evident with further incubation up to 72 h. With shorter incubation time (< or = 24 h) or at a lower Ang II concentration (< 10 mumol/L), such changes failed to occur. This effect of Ang II could be abolished by losartan (10 mumol/L), verapamil (1 mumol/L) or staurosporine (10 nmol/L). The above results indicate that Ang II-induced apoptosis in ARVMs may be mainly mediated by Ang II type I (AT1) receptors with [Ca2+]i and protein kinase C (PKC) playing a critical role.
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Laboratory of Molecular Pharmacology, Hunan Medical University, Changsha 410078.
Guo
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D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D006352:Heart Ventricles; D008297:Male; D009206:Myocardium / Q000166:cytology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism
D011945:Receptors, Angiotensin; D000804:Angiotensin II