Angiotensin II induces a rapid and transient increase of reactive oxygen species.
Vascular smooth muscle cells (VSMC) exhibit a hypertrophic and contractile response after angiotensin II (Ang II) treatment, and the NADH/NADPH oxidase-dependent synthesis of hydrogen peroxide (H(2)O(2)) seems to play a central role in these responses. Present experiments were designed to analyze the mechanisms responsible for the rapid changes induced by Ang II in the intracellular H(2)O(2) concentration in VSMC. Ang II induced a quick and transient increase of dichlorodihydrofluorescein (DCHF) fluorescence in VSMC, an effect that was completely abolished by catalase and by diethyldithiocarbamate, a cell-permeable superoxide dismutase inhibitor. Losartan and pertussis toxin prevented the stimulatory effect of Ang II. Both diphenylene iodonium (NADH/NADPH oxidase blocker) and 3-(4-octadecylbenzoyl)acrylic acid (phospholipase A2 blocker) inhibited the changes in DCHF fluorescence induced by Ang II, in a dose-dependent fashion, and the effects of both inhibitors were additive. These data demonstrate that Ang II induces a very quick and transient increase of H(2)O(2) in VSMC. This effect depends on the receptor type 1, is linked to a G protein, and involves both NADH/NADPH oxidase and phospholipase A2 activation. The mechanism may be related to the previously proposed role of H(2)O(2) in the genesis of the Ang II-induced cell contraction.
Rodríguez-Puyol
M
M
Department of Physiology, Alcalá University, Madrid, Spain. manuel.rodriguez@uah.es
Griera-Merino
M
M
Pérez-Rivero
G
G
Díez-Marqués
M L
ML
Ruiz-Torres
M P
MP
Rodríguez-Puyol
D
D
D000179:Acrylates / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001565:Benzoates; D002374:Catalase / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D004050:Ditiocarb / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005452:Fluoresceins / Q000737:chemistry / Q000378:metabolism; D005453:Fluorescence; D006861:Hydrogen Peroxide / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000179:Acrylates; D001565:Benzoates; D004791:Enzyme Inhibitors; D005452:Fluoresceins; D009861:Onium Compounds; D017382:Reactive Oxygen Species; D000804:Angiotensin II; C069438:3-(4-octadecyl)benzoylacrylic acid; C007517:diphenyleneiodonium; D004050:Ditiocarb; D006861:Hydrogen Peroxide; D002374:Catalase; D009247:NADH, NADPH Oxidoreductases; D037342:Pertussis Toxin; D010741:Phospholipases A; D054467:Phospholipases A2; D019808:Losartan; D007213:Indomethacin