Anti-aldosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism

Christian G. Brilla, Luiz S. Matsubara, Karl Weber

Research output: Contribution to journalArticle

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Abstract

In arterial hypertension associated with primary or secondary hyperaldosteronism myocardial fibrosis in an important determinant of pathologic hypertrophy. To further examine the relationship between elevations in plasma aldosterone (ALDO) and myocardial fibrosis, we analysed perivascular collagen area (PVCA) and interstitial collagen volume fraction (CVF) by videodensitometry and hydroxyproline concentration (HPro) by high-performance liquid chromatography. We examined both the left (LV) and right (RV) ventricles in the following rats models of primary or secondary hyperaldosteronism of eitht weeks duration: unilateral renal ischemia (RHT); continuous ALDO administration via osmotic minipumps (0.75 μg/h s.c.) and enhanced dietary sodium following uninephrectomy (AL); in RHT and AL after pre- and continuous treatment with either 20 (S) or 200 (SS) mg/kg/day s.c. of the aldosterone receptor antagonist, spironolactone; in AL after pre- and continuous treatment with 50 mg/kg/day oral captorpil (AL+CAP); as well as in age and sex matched controls (C). Systolic arterial pressure was comparably elevated in RHT and AL (202 ± 12 and 193 ± 7 mmHg, respectively; P < 0.0005 vs C); it remained elevated with low dose spironolactone in either model of arterial hypertension, but was normalized with high dose spironolactone or captopril in AL. Left ventricular hypertrophy (LVH), expressed as significantly elevated LV/RV weight or LV/BW ratios, was present in all experimental groups, excluding AL+SS and AL+CAP, when compared with C (P < 0.005). In each ventricle, CVF and PVCA were increased (P < 0.005) in either model of hypertension and in AL+CAP, but were no different from C in all groups receiving either dose of spironolactone. Similar findings were observed for HPro. Thus, myocardial fibrosis was comparable in primary or secondary hyperaldosteronism, wherein elevations in plasma aldosterone, relative to increased sodium intake, are associated with arterial hypertension. The compettive ALDO receptor antagonist, spironolactone, was able to prevent fibrosis in either model irrespective of the development of LVH and the presence of hypertension. Captopril prevented hypertension and LVH, but not unexpectedly it did not prevent myocardial fibrosis in primary hyperaldosteronism. These findings provide further evidence that in these rat models increased plasma ALDO, relative to dietary sodium, plays a major role in the adverse accumulation of collagen that appears in the myocardium.

Original languageEnglish (US)
Pages (from-to)563-575
Number of pages13
JournalJournal of Molecular and Cellular Cardiology
Volume25
Issue number5
DOIs
StatePublished - Jan 1 1993
Externally publishedYes

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Hyperaldosteronism
Spironolactone
Aldosterone
Fibrosis
Hypertension
Collagen
Left Ventricular Hypertrophy
Mineralocorticoid Receptor Antagonists
Dietary Sodium
Captopril
Hydroxyproline
Hypertrophy
Heart Ventricles
Myocardium
Arterial Pressure
Ischemia
Sodium
High Pressure Liquid Chromatography
Blood Pressure
Kidney

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Anti-aldosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism. / Brilla, Christian G.; Matsubara, Luiz S.; Weber, Karl.

In: Journal of Molecular and Cellular Cardiology, Vol. 25, No. 5, 01.01.1993, p. 563-575.

Research output: Contribution to journalArticle

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