Antifibrotic effects of spironolactone in preventing myocardial fibrosis in systemic arterial hypertension

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

Research output: Contribution to journalArticle

245 Citations (Scopus)

Abstract

Activation of the renin-angiotensin-aldosterone system in arterial hypertension can lead to remodeling of the myocardial collagen network, with progressive collagen accumulation in the cardiac interstitium. This reactive myocardial fibrosis, which is not secondary to myocyte necrosis, appears to be an important determinant of diastolic dysfunction and thus of pathologic hypertrophy. To examine the effects of the aldosterone antagonist spironolactone on myocardial fibrosis, we analyzed interstitial fibrosis in 7 different models of arterial hypertension in rats: 2 kidney, 1 clip model of renovascular hypertension (RHT); continuous subcutaneous aldosterone (0.75 μg/hr) infusion; RHT and aldosterone models treated with 20 mg/kg per day of subcutaneous spironolactone; uninephrectomized rats on a high sodium diet; and age- and sex-matched controls with or without spironolactone treatment. Systolic arterial pressure was comparably elevated in RHT and aldosterone models; it was modestly lowered but not normalized by 8 weeks of spironolactone treatment at the low doses used. Such treatment also failed to prevent left ventricular hypertrophy (LVH) in all experimental groups with hypertension. Spironolactone, however, was able to prevent myocardial fibrosis in RHT and aldosterone models of acquired arterial hypertension irrespective of the development of LVH and the presence of hypertension. These findings provide further evidence that elevated aldosterone levels play an important rote in the adverse remodeling of the myocardium in arterial hypertension. The antifibrotic effects of spironolactone, if confirmed in human studies, may be a valuable strategy in treating hypertensive heart disease.

Original languageEnglish (US)
JournalThe American journal of cardiology
Volume71
Issue number3
DOIs
StatePublished - Jan 21 1993
Externally publishedYes

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Spironolactone
Aldosterone
Renovascular Hypertension
Fibrosis
Hypertension
Left Ventricular Hypertrophy
Collagen
Mineralocorticoid Receptor Antagonists
Renin-Angiotensin System
Surgical Instruments
Muscle Cells
Hypertrophy
Heart Diseases
Myocardium
Arterial Pressure
Necrosis
Sodium
Diet
Blood Pressure
Kidney

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Antifibrotic effects of spironolactone in preventing myocardial fibrosis in systemic arterial hypertension. / Brilla, Christian G.; Matsubara, Luiz S.; Weber, Karl.

In: The American journal of cardiology, Vol. 71, No. 3, 21.01.1993.

Research output: Contribution to journalArticle

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