Pressure promotes angiotensin II--mediated migration of human coronary smooth muscle cells through increase in oxidative stress.
Angiotensin II--mediated oxidative stress may play a role in the pathogenesis of coronary atherosclerosis. We examined the effects of pressure on the angiotensin II--mediated increase in oxidative stress and migration of cultured human coronary smooth muscle cells (SMCs). Increased pressure (100 mm Hg) by helium gas for 48 hours increased angiotensin II--mediated oxidative stress as evaluated by flow cytometry and SMC migration (from 15.9 +/- 2.2 to 32.0 +/- 2.4 cells per 4 high-power fields, P<0.05; n=8). The pressure-induced increases in oxidative stress observed appear to involve phospholipase D (PLD) and protein kinase C (PKC), inasmuch as the indirect PLD inhibitor suramin, at 100 micromol/L, and the PKC inhibitor chelerythrine, at 1 micromol/L, completely blocked the increase in angiotensin II--mediated oxidative stress induced by pressure. Pressure-induced increase in angiotensin II--mediated oxidative stress was inhibited by diphenylene iodonium chloride, an NADPH oxidase inhibitor, by 79% (P<0.05, n=8). Losartan (1 micromol/L), its active metabolite E3174 (1 micromol/L), and the antioxidant N-acetylcysteine (100 mmol/L) but not PD123319 (1 micromol/L) also blocked pressure-induced increases in angiotensin II--mediated oxidative stress and SMC migration (P<0.05, n=8). These findings suggest a novel cellular mechanism whereby pressure regulates the angiotensin II--mediated migration of SMCs, possibly via angiotensin II type 1 receptors, and which involves PLD-mediated, PKC-mediated, and NADPH oxidase--mediated increases in oxidative stress.
Yasunari
Kenichi
K
Department of Cardiology, Graduate School of Medicine, Osaka City University, Osaka, Japan. yasunari@osaka.med.or.jp
Maeda
Kensaku
K
Nakamura
Munehiro
M
Yoshikawa
Junichi
J
D000804:Angiotensin II / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D003331:Coronary Vessels / Q000166:cytology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D010739:Phospholipase D / Q000502:physiology; D011312:Pressure; D011493:Protein Kinase C / Q000502:physiology
D000804:Angiotensin II; D011493:Protein Kinase C; D010739:Phospholipase D