Myocyte death in streptozotocin-induced diabetes in rats in angiotensin II- dependent.
To determine whether myocyte death and angiotensin II (AT II) formation are implicated in the development of diabetic cardiomyopathy, rats were injected with streptozotocin, and apoptosis and necrosis were measured at 3, 10, and 28 days. Expression of the components of the renin-angiotensin system (RAS) and AT II levels were assessed at 3 days. The percentage of AT II-labeled myocytes and the number and distribution of AT II sites in myocytes were measured at 3 and 10 days. The effects of AT1 blockade on local RAS and cell death were examined at 3 days. Diabetes was characterized by myocyte apoptosis that peaked at 3 days and decreased at 10 and 28 days, in spite of high concentrations of blood glucose. Cell necrosis was absent throughout. Angiotensinogen, renin, and AT1 receptor increased in myocytes from diabetic rat hearts, while angiotensin-converting enzyme and AT2 remained constant. AT II quantity increased severalfold, as did the fraction of AT II positive cells and the number of AT II sites per myocyte. However, AT II labeling decreased at 10 days, which paralleled the reduction in myocyte death. AT1 antagonist inhibited upregulation of this receptor and angiotensinogen, which prevented AT II synthesis and myocyte death at their peaks with diabetes. An aggregate 30% myocyte loss and a 14% increase in the volume of viable cells were found in diabetic rats at 28 days. Thus diabetic cardiomyopathy may be viewed as an AT II-dependent process in which that peptide plays a critical role in myocyte death and hypertrophy.
Fiordaliso
F
F
Department of Medicine, New York Medical College, Valhalla, USA.
Li
B
B
Latini
R
R
Sonnenblick
E H
EH
Anversa
P
P
Leri
A
A
Kajstura
J
J
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism; D013311:Streptozocin / Q000633:toxicity
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D013311:Streptozocin