Angiotensin II-induced hypertrophy of adult rat cardiomyocytes is blocked by nitric oxide.
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.
Ritchie
R H
RH
Program in Molecular and Cellular Cardiology, Department of Internal Medicine, Wayne State University and Detroit Veterans Affairs Medical Center, Detroit Michigan 48201, USA.
Schiebinger
R J
RJ
LaPointe
M C
MC
Marsh
J D
JD
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D006332:Cardiomegaly; D002478:Cells, Cultured; D018920:Coculture Techniques; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D016285:Iloprost / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010649:Phenylalanine / Q000378:metabolism; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D019323:omega-N-Methylarginine / Q000494:pharmacology
D020030:Nitric Oxide Donors; D000804:Angiotensin II; D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D010649:Phenylalanine; C002385:linsidomine; D008981:Molsidomine; D006152:Cyclic GMP; D016285:Iloprost; D001920:Bradykinin; D015056:1-Methyl-3-isobutylxanthine; D007213:Indomethacin