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 F-2-isopretane by 77%. Increased pressure also increased the activities of phospholipase D (PLD)), and particulate protein kinase C (PKC). The PLD inhibitor suramin 100 mumol/l, 1-butanol 40 mmol/l, and the PKC inhibitors chelerythrine 1 mumol/l and calphostin C 100 nmol/l and completely blocked the increase in oxidative stress induced by pressure. Carvedilol 1 mumol/l but not propranolol 1 mumol/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.