title: Gender differences in the development of uremic cardiomyopathy following partial nephrectomy: Role of progesterone.
abstract: Gender difference has been suggested as a risk factor for developing cardiovascular and renal diseases in humans and experimental animals. As a major sex hormone, progesterone was reported to compete with cardiotonic steroid binding to Na/K-ATPase. Our previous publication demonstrated that cardiotonic steroids (e.g., marinobufagenin) play an important role in the development of experimental uremic cardiomyopathy. We also observed that the putative mineralocorticoid antagonists, spironolactone and its major metabolite canrenone, antagonize binding of cardiotonic steroids to Na/K-ATPase in a competitive manner and also ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy. In the following studies, we noted that progesterone displayed competitive inhibition of cardiotonic steroid binding to Na/K-ATPase and partially inhibited collagen synthesis induced by marinobufagenin in cultured cardiac fibroblasts. Therefore, we sought to examine whether female rats displayed less uremic cardiomyopathy than male rats when subjected to partial nephrectomy. Although partial nephrectomy caused the induction of smaller increases in blood pressure of female rats, they appeared to be similarly susceptible to cardiac remodeling induced by partial nephrectomy in terms of hypertrophy and fibrosis as age-matched male rats. The possible explanations for our findings are therefore discussed.
authors.affiliation: Department of Medicine, University of Toledo, Ohio, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Drummond
authors.affiliation: Department of Medicine, University of Toledo, Ohio, USA.
authors.forename: George
authors.initials: G
authors.lastname: Buddny
authors.affiliation: Department of Medicine, University of Toledo, Ohio, USA.
authors.forename: Steven T
authors.initials: ST
authors.lastname: Haller
authors.affiliation: Marshall University Joan C. Edwards School of Medicine, Huntington, WV, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Marshall University Joan C. Edwards School of Medicine, Huntington, WV, USA.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Physiology/Pharmacology, University of Toledo College of Medicine, Toledo, OH, USA.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Medicine, University of Toledo, Ohio, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Malhotra
authors.affiliation: Marshall University Joan C. Edwards School of Medicine, Huntington, WV, USA.
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Shapiro
authors.affiliation: Department of Medicine, University of Toledo, Ohio, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Tian
keywords: Cardiotonic steroids; Collagen; Fibrosis; Gender; Progesterone; Renal failure; Uremic cardiomyopathy