J Korean Med Sci.  2008 Dec;23(6):1039-1045. 10.3346/jkms.2008.23.6.1039.

Expression of NAD(P)H Oxidase Subunits and Their Contribution to Cardiovascular Damage in Aldosterone/Salt-Induced Hypertensive Rat

Affiliations
  • 1Samsung Biomedical Research Institutue, Seoul, Korea.
  • 2Ottawa Health Research Institute, University of Ottawa, Ottawa, Canada.
  • 3Department of Medicine/Cardiology, Cheil General Hospital, Kwandong University College of Medicine, Seoul, Korea. parkjb@skku.edu

Abstract

NAD(P)H oxidase plays an important role in hypertension and its complication in aldosterone-salt rat. We questioned whether NAD(P)H oxidase subunit expression and activity are modulated by aldosterone and whether this is associated with target- organ damage. Rats were infused with aldosterone (0.75 microgram/hr/day) for 6 weeks and were given 0.9% NaCl+/-losartan (30 mg/kg/day), spironolactone (200 mg/kg/ day), and apocynin (1.5 mM/L). Aldosterone-salt hypertension was prevented completely by spironolactone and modestly by losartan and apocynin. Aldosterone increased aortic NAD(P)H oxidase activity by 34% and spironolactone and losartan inhibited the activity. Aortic expression of the subunits p47(phox), gp91(phox), and p22(phox) increased in aldosterone-infused rats by 5.5, 4.7, and 3.2-fold, respectively, which was decreased completely by spironolactone and partially by losartan and apocynin. Therefore, the increased expression of NAD(P)H oxidase may contribute to cardiovascular damage in aldosterone-salt hypertension through the increased expression of each subunit.

Keyword

Aldosterone; Oxidative Stress; NAD(P)H Oxidase; Hypertension

MeSH Terms

Acetophenones/administration & dosage
Aldosterone/administration & dosage/*toxicity
Aldosterone Antagonists/administration & dosage
Angiotensin II Type 1 Receptor Blockers/administration & dosage
Animals
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage
Aorta/metabolism/pathology
Blood Pressure/drug effects
Hypertension/chemically induced/drug therapy/*enzymology
Kidney/metabolism/pathology
Losartan/administration & dosage
Male
NADPH Oxidase/antagonists & inhibitors/*metabolism
Organ Size
Oxidative Stress
Protein Subunits/metabolism
RNA, Messenger/metabolism
Rats
Rats, Sprague-Dawley
Sodium Chloride/administration & dosage
Spironolactone/administration & dosage
Superoxides/metabolism
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