title: Excess aldosterone under normal salt diet induces cardiac hypertrophy and infiltration via oxidative stress.
abstract: Aldosterone is known to play a role in the pathophysiology of some cardiovascular diseases. However, previous studies on aldosterone infusion have been mostly performed in animals receiving sodium loading and uninephrectomy, and thus the cardiac action of aldosterone alone remains to be fully clarified. The present study was undertaken to investigate the direct cardiac action of aldosterone infusion alone in rats not subjected to salt loading and uninephrectomy. Aldosterone (0.75 microg/h) was subcutaneously infused into rats via an osmotic minipump for 14 days. Aldosterone infusion, under a normal salt diet, induced only a slight increase in the blood pressure of normal rats throughout the infusion. However, aldosterone significantly induced cardiac hypertrophy, as shown by echocardiography and measurement of cardiomyocyte cross-sectional area. Furthermore, aldosterone caused not only cardiac interstitial macrophage infiltration but also cardiac focal inflammatory lesions, which were associated with an increase in cardiac monocyte chemoattractant protein-1 (MCP-1) and osteopontin mRNA. The slight elevation of blood pressure by aldosterone infusion was completely prevented by tempol, the superoxide dismutase mimetic. However, tempol failed to suppress cardiac hypertrophy, the formation of inflammatory lesions, and upregulation of cardiac MCP-1 and osteopontin by aldosterone, while N-acetylcysteine could inhibit all of them. Our data provide evidence that aldosterone alone can induce cardiac hypertrophy and severe inflammatory response in the heart, independently of blood pressure, even in the absence of salt loading or nephrectomy. Aldosterone seems to induce cardiac inflammation and gene expression via oxidative stress that is inhibited by N-acetylcysteine but not by tempol.
authors.affiliation: Department of Pharmacology, Osaka City University Graduate School of Medical Science, Osaka, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Yoshida
authors.forename: Shokei
authors.initials: S
authors.lastname: Kim-Mitsuyama
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Wake
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Izumiya
authors.forename: Yasukatsu
authors.initials: Y
authors.lastname: Izumi
authors.forename: Tokihito
authors.initials: T
authors.lastname: Yukimura
authors.forename: Makiko
authors.initials: M
authors.lastname: Ueda
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwao
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000450:Aldosterone / Q000097:blood / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000235:genetics; D004452:Echocardiography; D006929:Hyperaldosteronism / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism*; D008297:Male; D009205:Myocarditis / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism; D053495:Osteopontin; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000235:genetics; D017673:Sodium Chloride, Dietary / Q000494:pharmacology
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D017673:Sodium Chloride, Dietary; C506897:Spp1 protein, rat; D053495:Osteopontin; D000450:Aldosterone; D000111:Acetylcysteine