Carvedilol inhibits pressure-induced increase in oxidative stress in coronary smooth muscle cells.
The cellular mechanisms by which hypertension enhances atherosclerosis are still not known in detail. Recently, evidence has been obtained that oxidative stress plays a role in the pathogenesis of pressure-induced atherosclerosis. We examined the effects of pressure on oxidative stress in cultured human coronary smooth muscle cells (SMCs). Application of increased pressure (+100 mmHg) with He gas for 48 h increased oxidative stress of measured by flow cytometry by 71% and F2-isopretane by 77%. Increased pressure also increased the activities of phospholipase D (PLD), and particulate protein kinase C (PKC). The PLD inhibitor suramin 100 micromol/l, 1-butanol 40 mmol/l, and the PKC inhibitors chelerythrine 1 micromol/l and calphostin C 100 nmol/l and completely blocked the increase in oxidative stress induced by pressure. Carvedilol 1 micromol/l but not propranolol 1 micromol/l blocked pressure-induced increases in oxidative stress in cultured SMCs. These findings suggest that pressure increases oxidative stress and that carvedilol significantly inhibits pressure-induced increase in oxidative stress in cultured human coronary smooth muscle cells.
Department of Cardiology, Graduate School of Medicine, Osaka City University, Japan. yasunari@osaka.med.or.jp
Kenichi
K
Yasunari
Kensaku
K
Maeda
Munehiro
M
Nakamura
Junichi
J
Yoshikawa
D000077214:Becaplermin; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015237:Dinoprost / Q000031:analogs & derivatives*; D028441:F2-Isoprostanes / Q000378:metabolism; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010739:Phospholipase D / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011312:Pressure; D011412:Propanolamines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D020574:Proto-Oncogene Proteins c-sis
D002227:Carbazoles; D028441:F2-Isoprostanes; D010982:Platelet-Derived Growth Factor; D011412:Propanolamines; D020574:Proto-Oncogene Proteins c-sis; D000077261:Carvedilol; D000077214:Becaplermin; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D011493:Protein Kinase C; D010739:Phospholipase D