Angiotensin II Stimulation In Vitro Induces Hypertrophy of Normal and Postinfarcted Ventricular Myocytes

From the Department of Medicine, New York Medical College, Valhalla.

Abstract—To determine whether angiotensin II (Ang II) stimulation of adult ventricular myocytes in vitro results in cellular hypertrophy, the changes in myocyte volume and protein content per cell were examined by confocal microscopy. Moreover, the possibility was considered that the upregulation of Ang II receptors on myocytes after infarction may potentiate and/or accelerate Ang II–mediated myocyte growth. Left ventricular myocytes isolated from control and failing hearts 3 days after infarction were cultured for 3 and 7 days in the presence of Ang II. Normal myocytes did not show an increase in volume and protein content at 3 days, but a 16% and 20% increase in these respective parameters was found at 7 days. Cell growth was faster and greater in myocytes from postinfarcted hearts. In these cells, myocyte volume increased 23% and protein content increased 28% at 3 days after Ang II administration. The higher hypertrophic reaction of myocytes from infarcted hearts occurred in spite of a 19% larger volume at isolation. In both groups of myocytes, the AT₁ receptor blocker losartan completely inhibited the consequences of Ang II. Conversely, the AT₂ receptor antagonist PD123319 had no effect on Ang II–induced hypertrophy. In conclusion, Ang II promotes myocyte growth through the activation of AT₁ receptors, which modulate the time and magnitude of this cellular response.

Key Words: angiotensin II • myocardial infarction • confocal microscopy • myocyte growth • protein content

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