Vol. 275, Issue 4, H1370-H1374, October 1998
Angiotensin II-induced hypertrophy of adult rat
cardiomyocytes is blocked by nitric oxide
Rebecca H.
Ritchie1,
Rick J.
Schiebinger1,
Margot C.
Lapointe2, and
James D.
Marsh1
1 Program in Molecular and
Cellular Cardiology, Department of Internal Medicine, Wayne State
University and Detroit Veterans Affairs Medical Center, Detroit
48201; and 2 Hypertension and
Vascular Research Unit, Henry Ford Hospital, Detroit, Michigan 48202
The aim of the present study was to test the
hypothesis that bradykinin-stimulated release of nitric oxide (NO)
and/or prostacyclin from endothelium blocks myocyte hypertrophy
in vitro. Angiotensin II increased
[3H]phenylalanine
incorporation by 21 ± 2% in myocytes cocultured with endothelial
cells; this was abolished by bradykinin in the presence of endothelial
cells. Bradykinin increased cytosolic concentrations of cGMP by 29 ± 4% in myocytes cocultured with endothelial cells. This was
abolished by inhibition of NO synthase and by a cyclooxygenase
inhibitor. Angiotensin II also increased [3H]phenylalanine
incorporation by 28 ± 3% in myocytes cultured in the absence of
endothelial cells. This effect of angiotensin II in monoculture was
abolished by donors of NO but not by bradykinin. Neither the stable
analog of prostacyclin (iloprost) nor the prostacyclin second messanger
analog 8-bromo-cAMP (8-BrcAMP) blocked the effect of angiotensin II.
Furthermore, 8-BrcAMP and iloprost individually increased
[3H]phenylalanine
incorporation. The antihypertrophic effects of bradykinin are
critically dependent on endothelium-derived NO.
angiotensin converting-enzyme inhibitors; bradykinin; prostacyclin; endothelium
