title: NAD(P)H oxidase activation by angiotensin II is dependent on p42/44 ERK-MAPK pathway activation in rat's vascular smooth muscle cells.
abstract: OBJECTIVE
  To determine whether the activation of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase and the increase of superoxide anion production by angiotensin II is dependent upon the activation of the ERK-MAPK pathway.
  
  
  METHODS
  Hypertension was induced in Sprague-Dawley rats by infusing angiotensin II (200 ng/kg per min) through osmotic pumps for 12 days. The effects of treatments including an angiotensin II type 1 (AT(1)) blocker losartan (20 mg/kg per day), a tyrosine kinase inhibitor genistein (1.6 microg/kg per min), a specific ERK-MAPK inhibitor, PD98059 (2 mg/kg per day) and an antioxidant alpha-lipoic acid (500 mg/kg of chow) were evaluated during angiotensin infusion. The aortic superoxide anion production, the ERK-MAPK pathway activity and the systolic blood pressure (SBP), were measured following those treatments.
  
  
  RESULTS
  Increases in the concentration of the superoxide anion (1622 to 3719 cpm), in NAD(P)H activity (107%) and in the ERK-MAPK activity (3.6-fold) in the aorta as well as a rise in the arterial pressure (136 to 184 mmHg) were observed 12 days after initiating the treatments (P < 0.05). When the angiotensin-treated rats were treated either with losartan, genistein, PD98059 or alpha-lipoic acid, increases in superoxide anion production, in NAD(P)H oxidase activity, in ERK-MAPK activity and in blood pressure were attenuated. A correlation between the superoxide anion production and the ERK-MAPK activity was also observed.
  
  
  CONCLUSIONS
  The present study suggests that the NAD(P)H-dependent increase of the superoxide anion production in the vascular tissue following a treatment with angiotensin II is dependent on the activation of the ERK-MAPK pathway.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Laplante
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.forename: Adil
authors.initials: A
authors.lastname: El Midaoui
authors.forename: Jacques
authors.initials: J
authors.lastname: de Champlain
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000037:antagonists & inhibitors; D019833:Genistein / Q000037:antagonists & inhibitors; D006973:Hypertension / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects* / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism*; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology*; D019255:NADPH Oxidases / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D004791:Enzyme Inhibitors; D005419:Flavonoids; D014662:Vasoconstrictor Agents; D013481:Superoxides; D000804:Angiotensin II; D008063:Thioctic Acid; D019833:Genistein; D019255:NADPH Oxidases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D019808:Losartan; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one