Increased carotid wall elastic modulus and fibronectin in aldosterone-salt-treated rats: effects of eplerenone.
BACKGROUND
Previous studies have demonstrated the development of cardiac fibrosis in aldosterone (Aldo)-salt hypertensive rats. Our aim was to determine the effects of Aldo and the Aldo receptor antagonist eplerenone (Epl) on in vivo mechanical properties of the carotid artery using echo-tracking system.


RESULTS
Aldo was administered (1 microg/h) in uninephrectomized Sprague-Dawley rats (SD) receiving a high-salt diet from 8 to 12 weeks of age. Uninephrectomized control SD rats received a normal salt diet without Aldo. Three groups of Aldo-salt rats were treated with 1, 10, or 30 mg/kg(-1) x d(-1) of Epl by gavage. Elasticity was measured by elastic modulus (Einc)-wall stress curves using medial cross-sectional area (MCSA). The structure of the arterial wall was analyzed by histomorphometry (elastin and collagen), immunohistochemistry (EIIIA fibronectin, Fn), and Northern blot (collagens I and III). Aldo produced increased systolic arterial pressure, pulse pressure, Einc, MCSA, and EIIIA Fn with no change in wall stress or elastin and collagen densities compared with controls without Aldo. No differences in collagen mRNA levels were detected between groups. Epl blunted the increase in pulse pressure in Aldo rats and normalized Einc-wall stress curves, MCSA, and EIIIA Fn. These effects were dose dependent and not accompanied by a reduction in wall stress.


CONCLUSIONS
Aldo is able to increase arterial stiffness associated with Fn accumulation, independently of wall stress. The preventive effects of Epl suggest a direct role for mineralocorticoid receptors in mechanical and structural alterations of large vessels in rat hyperaldosteronism.
Lacolley
Patrick
P
INSERM EMI U0107, Paris, France.
Labat
Carlos
C
Pujol
Alex
A
Delcayre
Claude
C
Benetos
Athanase
A
Safar
Michel
M
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015152:Blotting, Northern; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000096:biosynthesis; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D024061:Collagen Type III / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004548:Elasticity / Q000187:drug effects; D004549:Elastin / Q000096:biosynthesis; D000077545:Eplerenone; D005353:Fibronectins / Q000032:analysis / Q000378:metabolism*; D006929:Hyperaldosteronism / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D009392:Nephrectomy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary / Q000494:pharmacology*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014463:Ultrasonography; D014654:Vascular Patency / Q000187:drug effects
D024042:Collagen Type I; D024061:Collagen Type III; D005353:Fibronectins; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D012982:Sodium, Dietary; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D003094:Collagen; D004549:Elastin