title: Effects of indapamide in rats with pressure overload left ventricular hypertrophy.
abstract: We studied the in vivo effects of the antihypertensive diuretic agent indapamide on left ventricular (LV) morphology in chronically pressure-overloaded rat hearts. LV pressure and subsequently LV mass were increased by banding the ascending aorta over a period of 6 weeks. Thereafter, animals were treated with low-dose (1 mg/kg/day, n = 9) or high-dose (10 mg/kg/day, n = 9) indapamide for another 6 weeks. Low-dose indapamide treatment reduced LV weights as compared with vehicle-treated controls (n = 9; -12%; p = 0.008). Furthermore, low-dose indapamide treatment resulted in a decrease of myocyte volume (59.0 +/- 10.6 vs. 79.0 +/- 9.8 m3 x 10(-27); p < 0.05) and an improvement of molecular markers of hypertrophy: a reduction of LV atrial natriuretic factor mRNA expression (-37%; p < 0.05), and an increase of the V1/V3 myosin ratio (+121%; p < 0.05). Low-dose indapamide also reduced significantly plasma (-65%) and LV angiotensin-converting enzyme (ACE) activities (-74%) as well as LV mRNA levels (-24%). These changes were observed despite continued pressure overload of the LV and despite a lack of significant changes in sodium excretion with the prolonged administration of low-dose indapamide. High-dose indapamide treatment showed no significant effects on LV mass, structure, and gene expression. Furthermore, high-dose indapamide increased plasma renin activity substantially, whereas low-dose treatment was without effect on circulating renin. In conclusion, in rats with continuous LV pressure-overload low-dose treatment with indapamide leads to mild regression of cardiac hypertrophy, accompanied by a downregulation of components of the cardiac renin-angiotensin system. These effects may be mediated by mechanisms apart from the known diuretic and antihypertensive actions of indapamide, because sodium excretion and blood pressure were stable with long-term treatment and are unlikely to be related to LVH regression in this model.
authors.affiliation: University of Regensburg, Klinik und Poliklinik für Innere Medizin II, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Böcker
authors.forename: H
authors.initials: H
authors.lastname: Hupf
authors.forename: D
authors.initials: D
authors.lastname: Grimm
authors.forename: K
authors.initials: K
authors.lastname: Kurzidim
authors.forename: H
authors.initials: H
authors.lastname: Schunkert
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001024:Aortic Valve Stenosis / Q000150:complications / Q000473:pathology; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003404:Creatinine / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000209:etiology; D007190:Indapamide / Q000627:therapeutic use*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D012313:RNA; D012964:Sodium; D003404:Creatinine; D007190:Indapamide; D011188:Potassium