title: Sex-linked differences in the course of chronic kidney disease and congestive heart failure: a study in 5/6 nephrectomized Ren-2 transgenic hypertensive rats with volume overload induced using aorto-caval fistula.
abstract: The role of hypertension and the renin-angiotensin system (RAS) in sex-related differences in the course of chronic kidney disease (CKD) and congestive heart failure (CHF) remain unclear, especially when the two diseases are combined. In male and female Ren-2 transgenic rats (TGR), a model of hypertension with activation of endogenous RAS, CKD was induced by 5/6 renal mass reduction (5/6 NX) and CHF was elicited by volume overload achieved by creation of an aorto-caval fistula (ACF). The primary aim of the study was to examine long-term CKD- and CHF-related mortality, especially in animals with CKD and CHF combined, with particular interest in the potential sex-related differences. The follow-up period was 23 weeks after the first intervention (5/6 NX). We found, first, that TGR did not exhibit sexual dimorphism in the course of 5/6 NX-induced CKD. Second, in contrast, TGR exhibited important sex-related differences in the course of ACF-induced CHF-related mortality: intact female TGR showed higher survival rate than male TGR. This situation is reversed in the course of combined 5/6 NX-induced CKD and ACF-induced CHF-related mortality: intact female TGR exhibited poorer survival than male TGR. Third, the survival rate in animals with combined 5/6 NX-induced CKD and ACF-induced CHF was significantly worsened as compared with rat groups that were exposed to 'single organ disease'. Collectively, our present results clearly show that CKD aggravates long-term mortality of animals with CHF. In addition, TGR exhibit remarkable sexual dimorphism with respect to CKD- and CHF-related mortality, especially in animals with combined CKD and CHF.
authors.affiliation: Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.|Department of Pathophysiology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Luděk
authors.initials: L
authors.lastname: Červenka
authors.affiliation: Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Škaroupková
authors.affiliation: Department of Renal and Body Fluid Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kompanowska-Jezierska
authors.affiliation: Department of Renal and Body Fluid Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Sadowski
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005402:Fistula / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D006333:Heart Failure / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology*; D006973:Hypertension / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D009392:Nephrectomy / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012083:Renin / Q000378:metabolism; D012727:Sex Characteristics; D015996:Survival Rate / Q000639:trends
chemical_list: C535029:Ren2 protein, rat; D012083:Renin
keywords: 5/6 nephrectomy; aorto-caval fistula; chronic kidney disease; congestive heart failure; hypertension; renin-angiotensin system; sex differences in rats