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.
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