title: Lack of cardiac fibrosis in a new model of high prorenin hyperaldosteronism.
abstract: The aim of the present study was to test the hypothesis that elevation of prorenin in plasma is sufficient to induce cardiac fibrosis. Normotensive cyp1a1ren-2 transgenic rats with normal plasma prorenin and aldosterone levels were given 0.125% indole-3-carbinol (I3C) orally for a period of 12 wk. Plasma prorenin and aldosterone levels were determined in 4-wk intervals, and cardiac marker enzymes for hypertrophy, fibrosis, and oxidative stress as well as cardiac pathology were investigated. In I3C-treated cyp1a1 ren-2 transgenic rats, plasma prorenin concentrations were >100-fold elevated (> or = 7.1 + or - 2.6 microg ANG I.ml(-1).h(-1) vs. < or = 0.07 + or - 0.1; P < 0.001), whereas active renin levels were suppressed (0.09 + or - 0.02 vs. 0.2 + or - 0.1; P < 0.05). Aldosterone concentrations were elevated three- to fourfold for a period of >4 wk (574 + or - 51 vs. 160 + or - 68 pg/ml; P < 0.01). After 12 wk of I3C, rats exhibited moderate cardiac hypertrophy (heart weight/body weight 2.5 + or - 0.04 vs. 3.1 + or - 0.1 mg/g; P < 0.01). There was a slight increase in mRNA contents of endothelin 1 (1.21 + or - 0.08 vs. 0.75 + or - 0.007; P < 0.001), NADP oxidase-2 (1.03 + or - 0.006 vs. 0.76 + or - 0.04; P < 0.001), transforming growth factor-beta (0.99 + or - 0.06 vs. 0.84 + or - 0.04; P < 0.05), collagen type I (1.32 + or - 0.32 vs. 0.94 + or - 0.18; P < 0.05), and intercellular adhesion molecule-1 (1.12 + or - 0.12 vs. 0.84 + or - 0.08; P < 0.05). These genes are known to be stimulated by the renin-angiotensin system. There were no histological signs of fibrosis in the heart. We found that prorenin and aldosterone alone are not sufficient to induce considerable cardiac fibrosis in the absence of sodium load.
authors.affiliation: Institute of Physiology, Univ. of Greifswald, Greifswalder Str. 11C, D-17495 Karlsburg, Germany. joerg.peters@uni-greifswald.de
authors.forename: Jörg
authors.initials: J
authors.lastname: Peters
authors.forename: Torsten
authors.initials: T
authors.lastname: Schlüter
authors.forename: Thomas
authors.initials: T
authors.lastname: Riegel
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Peters
authors.forename: Andreas
authors.initials: A
authors.lastname: Beineke
authors.forename: Ulrike
authors.initials: U
authors.lastname: Maschke
authors.forename: Norbert
authors.initials: N
authors.lastname: Hosten
authors.forename: John J
authors.initials: JJ
authors.lastname: Mullins
authors.forename: Rainer
authors.initials: R
authors.lastname: Rettig
mesh_terms: D000284:Administration, Oral; D000450:Aldosterone / Q000097:blood; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D024042:Collagen Type I / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005355:Fibrosis; D006929:Hyperaldosteronism / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007211:Indoles / Q000008:administration & dosage; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic; D012083:Renin / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D024042:Collagen Type I; D019332:Endothelin-1; D007211:Indoles; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C473112:Ren2 protein, mouse; D016212:Transforming Growth Factor beta; D018799:Intercellular Adhesion Molecule-1; D000450:Aldosterone; C016517:indole-3-carbinol; D019363:Cytochrome P-450 CYP1A1; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D048049:Extracellular Signal-Regulated MAP Kinases; D012083:Renin