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EXPERIMENTAL STUDY

Prevention of aortic and cardiac fibrosis by spironolactone in old normotensive rats

^a Department of Internal Medicine and INSERM U337, Broussais Hospital, Paris, France

Manuscript received May 8, 2000; revised manuscript received August 18, 2000, accepted October 2, 2000.

Reprint requests and correspondence: Dr. Michel Safar, Médecine Interne 1, Hôpital Broussais, 96 rue Didot, 75674 Paris Cedex 14, France
michel.safar{at}brs.ap-hop-paris.fr

OBJECTIVES

Because the synthesis of aldosterone is mainly modulated by angiotensin II through type I receptor stimulation and because converting enzyme inhibition (CEI) does not modify aortic extracellular matrix in old normotensive rats, the aim of the present study was to determine whether inhibition of aldosterone formation was able to prevent aortic fibrosis in old Sprague-Dawley normotensive rats.

BACKGROUND

We have previously shown that long-term aldosterone antagonism prevents the age-related increase in aortic collagen accumulation in young spontaneously hypertensive rats, independent of blood pressure changes. In contrast, we reported that the positive effects of CEI in the prevention of aortic collagen accumulation were related to the inhibition of angiotensin II actions on angiotensin II type I receptors.

METHODS

For this purpose, we studied the histomorphometric and stiffness (echo-tracking technique) changes of an eight-week treatment with the aldosterone antagonist spironolactone by comparison with placebo.

RESULTS

At the end of treatment, spironolactone in conscious animals did not change intra-arterial blood pressure, aortic and carotid wall thickness, and cardiac weight. Cardiac collagen density and, to a lesser extent, carotid collagen and elastin densities and contents were significantly decreased in association with an increase of carotid distensibility.

CONCLUSIONS

These results show that in old normotensive rats, spironolactone can markedly prevent cardiac and, to a lesser extent, arterial fibrosis and improve arterial stiffness, despite a lack of hypotensive effect.

Abbreviations and Acronyms   CEI = converting enzyme inhibition   CSA = cross-sectional area   P = change in pulse pressure   PP = pulse pressure   SHRs = spontaneously hypertensive rats

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