Endothelins and myocardial fibrosis.
BACKGROUND
Endothelins are associated with cardiac remodeling. These peptides are the most powerful vasoconstrictor described-whether this remodeling is a direct effect of this hormone or indirect response to a relative ischemia promoted by vasoconstrictor effect. We evaluated the role of endothelin upon myocardial fibrosis despite of its hemodynamic effects and the benefits of its antagonism.


RESULTS
We used 40 Wistar rats: control, sham operated, rats had undergone myocardial infarction (MI) and MI rats treated with SB209670 which is an ET(A)/ET(B) endothelin antagonist. We evaluated tail systolic blood pressure (BP) and left ventricular end diastolic pressure (LVED) before surgery, just after, and at the end of the study. Remodeling was studied based on interstitial collagen and MI size by an image system analysis. BP decreased in MI groups after surgery, but did not differ between treated and untreated animals. LVED had increased levels in MI groups after surgery and did not differ between them. However, ICVF had an increase in MI group but significantly less in MI+SB209670. MI size was similar in both groups.


CONCLUSIONS
Endothelin may have a pivotal role in the myocardial fibrosis by direct stimulation of collagen accumulation despite of its hemodynamic effects.
Ramires
Felix J A
FJ
Heart Institute (InCor)-University of São Paulo Medical School, São Paulo, Brazil.
Nunes
Vera L
VL
Fernandes
Fabio
F
Mady
Charles
C
Ramires
José A F
JA
D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D005355:Fibrosis; D007189:Indans / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007189:Indans; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-; D003094:Collagen