Prevention of aortic and cardiac fibrosis by spironolactone in old normotensive rats.
OBJECTIVE
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.
Lacolley
P
P
Department of Internal Medicine and INSERM U337, Broussais Hospital, Paris, France.
Safar
M E
ME
Lucet
B
B
Ledudal
K
K
Labat
C
C
Benetos
A
A
D000367:Age Factors; D000450:Aldosterone / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology*; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D004719:Endomyocardial Fibrosis / Q000473:pathology / Q000503:physiopathology*; D005355:Fibrosis; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013148:Spironolactone / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology
D013148:Spironolactone; D000450:Aldosterone