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: W Böcker, H Hupf, D Grimm, K Kurzidim, H Schunkert
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 36 Issue 4 Pg. 481-6 (Oct 2000) ISSN: 0160-2446 [Print] United States
• PMID: 11026649 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Biomarkers
• RNA
• Sodium
• Creatinine
• Indapamide
• Potassium

Topics

• Animals
• Antihypertensive Agents (therapeutic use)
• Aortic Valve Stenosis (complications, pathology)
• Biomarkers
• Blood Pressure (drug effects, physiology)
• Creatinine (metabolism)
• Heart (drug effects)
• Hypertension (complications, drug therapy)
• Hypertrophy, Left Ventricular (drug therapy, etiology)
• Indapamide (therapeutic use)
• Male
• Organ Size (drug effects)
• Potassium (metabolism)
• RNA (biosynthesis, genetics)
• Rats
• Rats, Wistar
• Renin-Angiotensin System (drug effects, physiology)
• Sodium (metabolism)
• Ventricular Function, Left (drug effects)