Mineralocorticoid excess, dietary sodium, and myocardial fibrosis

Christian G. Brilla, Karl Weber

Research output: Contribution to journalArticle

407 Citations (Scopus)

Abstract

Unlike the non-renin-dependent hypertension associated with infrarenal aorta banding, an abnormal accumulation of fibrillar collagen occurs within the adventitia of intramural coronary arteries and neighboring interstitial space of the left and right ventricles in arterial hypertension associated with primary or secondary hyperaldosteronism. Based on these findings it was suggested that this interstitial and perivascular fibrosis was mediated by mineralocorticold excess (i.e., elevated plasma aldosterone relative to dietary sodium) and not ventricular loading. To further address the importance of mineralocorticoid excess, we examined the fibrous tissue response after 8 weeks in the following uninephrectomized rat groups receiving a high-sodium diet: d-aldosterone (ALDO) infusion (0.75 μg/hr sc, n = 16); deoxycorticosterone acetate (DOCA) administration (100 mg/kg/wk sc, n = 8); and administration of a mineralocorticoid-like substance, glycyrrhizic acid (GA; 1 gm kg/wk sc, n = 8). Compared with ALDO infusion and sodium deprivation (n = 9), untreated controls (n = 14), and uninephrectomized rats with high dietary sodium and no mineralocorticoid administration (n = 15), we found (1) hypertension and left ventricular hypertrophy with all forms of mineralocorticoid excess; (2) a rise in collagen volume fraction with ALDO, and an increase in perivascular collagen with DOCA; and (3) no observance of myocardiol fibrosis with GA or experimental controls, including ALDO infusion and sodium deprivation. Thus, in the presence of enhanced sodium intake, chronic administration of ALDO or DOCA are associated with collagen accumulation in the myocardium, whereas with the mineralocorticoid-like compound GA, myocardial fibrosis was not seen. The cellular mechanisms responsible for myocardial fibrosis in mineralocorticoid excess appear to be linked to a mineralocorticoid-mediated sodium overload of cardiac fibroblasts that are responsible for the synthesis of the major fibrillar collagens in the heart.

Original languageEnglish (US)
Pages (from-to)893-901
Number of pages9
JournalThe Journal of Laboratory and Clinical Medicine
Volume120
Issue number6
StatePublished - Jan 1 1992
Externally publishedYes

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Dietary Sodium
Mineralocorticoids
Aldosterone
Fibrosis
Sodium
Desoxycorticosterone
Fibrillar Collagens
Acetates
Collagen
Hypertension
Heart Ventricles
Rats
Glycyrrhizic Acid
Adventitia
Hyperaldosteronism
Left Ventricular Hypertrophy
Fibroblasts
Nutrition
Aorta
Volume fraction

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Mineralocorticoid excess, dietary sodium, and myocardial fibrosis. / Brilla, Christian G.; Weber, Karl.

In: The Journal of Laboratory and Clinical Medicine, Vol. 120, No. 6, 01.01.1992, p. 893-901.

Research output: Contribution to journalArticle

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