Angiotensin II does not induce apoptosis but rather prevents apoptosis in cardiomyocytes.
The ability of angiotensin II (ang II) to produce apoptosis is controversial. Cardiomyocytes, isolated from 7-day embryonic chick hearts and maintained in culture for 72 h, were treated with ang II. There was no evidence of ang II-induced apoptosis consistently demonstrated by six different techniques: electrophoretic separation of fragmented DNA, staining with TUNEL, enzyme-linked immunosorbent assay specific for fragmented DNA, dual staining of cells with fluorescein diacetate and propidium iodide with analysis by flow cytometry, staining of nuclei with propidium iodide and cell microscopy. In contrast, apoptosis was readily induced by camptothecin or staurosporine or serum deprivation. The absence of ang II-induced cell death was also demonstrated in neonatal mouse cardiomyocytes in culture. We further sought to answer the question whether ang II Type 1 receptor blockade by antagonizing the potential beneficial effects mediated through this receptor and producing more ang II binding to the ang II Type 2 receptors, would lead to cardiac apoptosis. There was no evidence of ang II-induced apoptosis in the presence of the ang II Type 1 receptor antagonist losartan in embryonic chick cardiomyocytes. Rather ang II prevented serum deprivation-induced apoptosis. In summary, in these cardiomyocytes ang II does not induce but rather prevents apoptosis.
Kong
J Y
JY
Department of Medicine (Cardiology), University of British Columbia, Vancouver, BC, Canada.
Rabkin
S W
SW
D000804:Angiotensin II / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002166:Camptothecin / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D002642:Chick Embryo; D016895:Culture Media, Serum-Free; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006321:Heart / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D051379:Mice; D009206:Myocardium / Q000166:cytology*; D009336:Necrosis; D011419:Propidium / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
D016895:Culture Media, Serum-Free; D013778:Tetrazolium Salts; D013844:Thiazoles; D000804:Angiotensin II; D011419:Propidium; C022616:thiazolyl blue; D019311:Staurosporine; D002166:Camptothecin