TY - JOUR T1 - Effects of Adrenomedullin on Cardiac Oxidative Stress and Collagen Accumulation in Aldosterone-Dependent Malignant Hypertensive Rats JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1323 LP - 1329 DO - 10.1124/jpet.106.105106 VL - 318 IS - 3 AU - Matlubur Rahman AU - Akira Nishiyama AU - Peng Guo AU - Yukiko Nagai AU - Guo-Xing Zhang AU - Yoshihide Fujisawa AU - Yu-Yan Fan AU - Shoji Kimura AU - Naohisa Hosomi AU - Koji Omori AU - Youichi Abe AU - Masakazu Kohno Y1 - 2006/09/01 UR - http://jpet.aspetjournals.org/content/318/3/1323.abstract N2 - We examined the effects of adrenomedullin on cardiac oxidative stress and collagen accumulation in aldosterone-dependent malignant hypertensive rats. Spontaneously hypertensive rats (SHRs) were treated with one of the following combinations for 4 weeks: tap water and vehicle [0.5% ethanol, subcutaneously (s.c.), n = 5], 1% NaCl in drinking water and vehicle (n = 8), 1% NaCl and aldosterone (0.75 μg/h s.c., n = 8), and 1% NaCl, aldosterone, and adrenomedullin (1.3 μg/kg/h s.c., n = 8). Systolic blood pressure (SBP) and left ventricular (LV) weight were higher in aldosterone-treated SHRs than vehicle- or vehicle/1% NaCl-treated SHRs. Thiobarbituric acid reactive substances (TBARS) levels and NADPH oxidase activity in LV tissues of aldosterone-treated SHRs were also higher than those of vehicle- or vehicle/1% NaCl-treated SHRs, and these changes were associated with increases in LV mRNA levels of p22phox, gp91phox, fibronectin, collagen types I and III, as well as collagen content. Treatment with adrenomedullin did not alter SBP or LV weight but attenuated aldosterone-induced increases in TBARS levels, NADPH oxidase activity, and mRNA levels of p22phox, gp91phox, fibronectin, collagen types I and III, as well as collagen content in LV tissues. These data suggest that NADPH oxidase-mediated reactive oxygen species production is involved in the pathogenesis of cardiac collagen accumulation in aldosterone-dependent malignant hypertensive rats and that the cardioprotective effects of adrenomedullin are mediated through the suppression of this pathway. The American Society for Pharmacology and Experimental Therapeutics ER -