Differences between cardiac and arterial fibrosis and stiffness in aldosterone-salt rats: effect of eplerenone.
BACKGROUND
Previous experiments have studied separately the development of either cardiac or aortic fibrosis and stiffness in aldosterone (Aldo)-salt hypertensive rats. Our aim was to determine in vivo the effects of Aldo and the Aldo receptor antagonist eplerenone (Epl) on simultaneous changes in cardiac and arterial structure and function and their interactions.


RESULTS
Aldo was administered in uninephrectomised Sprague-Dawley rats receiving a high-salt diet from 8 to 12 weeks of age. Three groups of Aldo-salt rats were treated with 1 to 100 mg/kg-1. d-1 Epl by gavage. Arterial elasticity was measured by elastic modulus (Einc)-wall stress curves using medial cross-sectional area (MCSA). The cardiac and arterial walls were analysed by histomorphometry (elastin and collagen), immunohistochemistry (EIIIA fibronectin, Fn), and Northern blot (collagens I and III). Aldo caused increased systolic blood pressure (SBP), carotid Einc, MCSA, and EIIIA Fn with no change in wall stress or elastin and collagen densities. No difference in collagen mRNA levels was detected between groups. During the same period, cardiac mass and collagen mRNA and protein levels increased markedly in the myocardial tissue. Epl normalised collagen in the myocardium, Eincwall stress curves, MCSA, and EIIIA Fn in Aldo rats. These dose-dependent effects were not accompanied by a consistent reduction in SBP and cardiac mass.


CONCLUSIONS
In exogenous hyperaldosteronism in the rat, Aldo causes independently myocardial collagen and arterial Fn accumulation, the latter being responsible for increased intrinsic carotid stiffness. Epl prevents both cardiac and arterial effects but does not reduce consistently SBP.
Nehme
Johnny
J
INSERM U572, Paris, France.
Mercier
Nathalie
N
Labat
Carlos
C
Benetos
Athanase
A
Safar
Michel E
ME
Delcayre
Claude
C
Lacolley
Patrick
P
D000818:Animals; D001011:Aorta / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D015152:Blotting, Northern; D002340:Carotid Artery Diseases / Q000209:etiology / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D000077545:Eplerenone; D005355:Fibrosis; D006331:Heart Diseases / Q000209:etiology* / Q000473:pathology*; D006973:Hypertension / Q000139:chemically induced / Q000150:complications* / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D009206:Myocardium / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014652:Vascular Diseases / Q000209:etiology* / Q000473:pathology*
D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D013148:Spironolactone; D000077545:Eplerenone; D003094:Collagen