Role of gp91phox-containing NADPH oxidase in the deoxycorticosterone acetate-salt-induced hypertension.
NADPH oxidase plays an important role in vascular oxidative stress in hypertensive diseases. We evaluated whether NADPH oxidase-dependent superoxide (O(2)(-)) production is involved in the deoxycorticosterone acetate (DOCA)-salt-induced hypertension, using mice which are genetically deficient in gp91phox, an NADPH oxidase subunit protein (gp91(-/-) mice). Two weeks after the DOCA-salt treatment, systolic blood pressure was significantly elevated in wild-type mice, but not in gp91(-/-) mice. After a 5-week treatment period, wild-type mice developed high blood pressure, with a systolic blood pressure of 127 +/- 3 mm Hg, compared with 107 +/- 4 mm Hg in gp91(-/-) mice. Aortic O(2)(-) production in wild-type DOCA-salt-treated mice was significantly higher than that in wild-type sham mice, whereas there were no significant differences in aortic O(2)(-) production between gp91(-/-) DOCA-salt-treated and sham mice. These findings suggest that vascular O(2)(-) overproduction via gp91phox-containing NADPH oxidase is one of the crucial factors in the development of DOCA-salt-induced hypertension.
Fujii
Aya
A
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Nakano
Daisuke
D
Katsuragi
Miyuki
M
Ohkita
Mamoru
M
Takaoka
Masanori
M
Ohno
Yukihiro
Y
Matsumura
Yasuo
Y
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone / Q000008:administration & dosage / Q000633:toxicity*; D005838:Genotype; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
D008562:Membrane Glycoproteins; D013481:Superoxides; D003900:Desoxycorticosterone; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases