Related Experiment Videos
Mineralocorticoid excess, dietary sodium, and myocardial fibrosis
1Division of Cardiology, University of Missouri-Columbia 65212.
Insights
Mineralocorticoid excess, such as aldosterone (ALDO) and deoxycorticosterone acetate (DOCA), causes hypertension and cardiac fibrosis in rats. However, glycyrrhizic acid (GA), a mineralocorticoid-like substance, did not induce myocardial fibrosis.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Pathology
Background:
- Arterial hypertension linked to hyperaldosteronism involves collagen accumulation in coronary arteries and ventricles.
- This fibrosis is hypothesized to be driven by mineralocorticoid excess rather than ventricular pressure overload.
Purpose of the Study:
- To investigate the role of mineralocorticoid excess in causing cardiac fibrosis.
- To compare the effects of aldosterone (ALDO), deoxycorticosterone acetate (DOCA), and glycyrrhizic acid (GA) on cardiac tissue in the presence of high sodium intake.
Main Methods:
- Uninephrectomized rats on a high-sodium diet were infused with D-aldosterone (ALDO), administered deoxycorticosterone acetate (DOCA), or given glycyrrhizic acid (GA).
- Control groups included untreated rats, rats with high sodium only, and rats receiving ALDO with sodium deprivation.
- Fibrous tissue response was assessed after 8 weeks.
Main Results:
- All mineralocorticoid excess groups (ALDO, DOCA) developed hypertension and left ventricular hypertrophy.
- ALDO infusion increased collagen volume fraction, while DOCA increased perivascular collagen.
- Glycyrrhizic acid (GA) and control groups did not exhibit myocardial fibrosis.
Conclusions:
- Chronic administration of ALDO or DOCA, in the context of high sodium intake, leads to collagen accumulation and myocardial fibrosis in rats.
- Mineralocorticoid-like compound GA does not induce myocardial fibrosis under similar conditions.
- These findings underscore the specific role of mineralocorticoid excess in mediating cardiac fibrosis.
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 mineralocorticoid 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 micrograms/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 myocardial 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.(ABSTRACT TRUNCATED AT 250 WORDS)