OBJECTIVETo study the effect of genistein on the expression of heme oxygenase-1 (HO-1) in rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT).

METHODSSixty male Sprague-Dawley rats were randomly divided into 4 groups (n=15), namely the control group, model group, low-dose (20 µg/kg) genistein group and high-dose (80 µg/kg) genistein group. The hemodynamic parameters were measured and the remodeling of pulmonary small arteries was observed by electron microscope (EM). The expression of HO-1 in the lung tissues were detected by Western blotting.

RESULTSCompared with the model group, genistein treatment significantly reduced the elevated mean pulmonary arterial pressure, improved the right ventricular hypertrophy index, and increased the expression of HO-1 in a dose-dependent manner.

CONCLUSIONGenistein attentuates pulmonary arterial hypertension in MCT-treated rats possibly by up-regulation of HO-1 in the lung tissues.

Animals ; Genistein ; pharmacology ; therapeutic use ; Heme Oxygenase (Decyclizing) ; metabolism ; Hypertension, Pulmonary ; chemically induced ; drug therapy ; enzymology ; Lung ; enzymology ; pathology ; Male ; Monocrotaline ; Rats ; Rats, Sprague-Dawley ; Up-Regulation ; drug effects

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