NAD(P)H oxidase inhibitor prevents blood pressure elevation and cardiovascular hypertrophy in aldosterone-infused rats.
Increased bioavailability of reactive oxygen species (ROS) has been implicated in the pathogenesis of mineralocorticoid hypertension. To find out the source of ROS, we evaluated the role of NAD(P)H oxidase in blood pressure (BP) elevation, cardiovascular hypertrophy, and fibrosis in aldosterone-salt rats. Aldosterone infusion (0.75 microg/h) significantly increased BP, which is attenuated by apocynin (1.5 mmol/L). Cardiac hypertrophy developed by aldosterone infusion was also normalized with apocynin. Greater mRNA for p22phox and NAD(P)H oxidase activity (more than twofold) in aorta of aldosterone-infused rats was reduced in apocynin-treated rats. Aldosterone infusion increased marginally procollagen I and III expression in LV compared to controls and apocynin decreased procollagen. Masson's Trichrome stain showed increased cardiac perivascular fibrosis, which was reduced by apocynin. These results suggest that NAD(P)H oxidase plays an important role in cardiovascular damage associated with mineralocorticoid hypertension.
Park
Young Mee
YM
Department of Medicine/Cardiology, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine and Samsung Biomedical Research Institute, Seoul, Republic of Korea.
Park
Mi Young
MY
Suh
Yeon-Lim
YL
Park
Jeong Bae
JB
D000098:Acetophenones / Q000494:pharmacology; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001011:Aorta / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D005355:Fibrosis; D006352:Heart Ventricles / Q000378:metabolism; D006973:Hypertension / Q000517:prevention & control*; D006984:Hypertrophy / Q000517:prevention & control*; D008297:Male; D026901:Membrane Transport Proteins; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019255:NADPH Oxidases; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000098:Acetophenones; D000959:Antihypertensive Agents; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000450:Aldosterone; D003094:Collagen; C056165:acetovanillone; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase