RT Journal Article
SR Electronic
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
FD American Society for Pharmacology and Experimental Therapeutics
SP 1323
OP 1329
DO 10.1124/jpet.106.105106
VO 318
IS 3
A1 Matlubur Rahman
A1 Akira Nishiyama
A1 Peng Guo
A1 Yukiko Nagai
A1 Guo-Xing Zhang
A1 Yoshihide Fujisawa
A1 Yu-Yan Fan
A1 Shoji Kimura
A1 Naohisa Hosomi
A1 Koji Omori
A1 Youichi Abe
A1 Masakazu Kohno
YR 2006
UL http://jpet.aspetjournals.org/content/318/3/1323.abstract
AB 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