Angiotensin II and structural remodeling of coronary vessels in rats.
A perivascular fibrosis of intramyocardial coronary arterioles, composed of type I fibrillar collagen, is associated with chronic elevations in circulating angiotensin II (AngII). The hypothesis tested herein is that coronary vascular remodelling involving cardiac interstitial fibroblasts is responsible for this fibrous tissue response. This morphologic study therefore had several objectives: (1) to determine whether a continuous infusion of AngII (150 ng/min/kg) would alter plasma fibronectin (pFN) labeling of coronary vessels, and to identify the level of the coronary vasculature involved in this response; (2) to determine whether the chronic administration of AngII would ultimately lead to enhanced type I collagen synthesis and a perivascular fibrosis of arterioles, and to identify the cellular response associated with this fibrogenesis. Accordingly, the hearts of rats receiving AngII over the course of 2 weeks were examined at 1, 2, 4, 7, 10, and 14 days. From the same heart, serial sections were obtained for pFN immunofluorescent microscopy, PCNA immunolabeling, in situ hybridization with a type I collagen probe, and light microscopy to address cellular response (hematoxylin and eosin) and formation of fibrillar collagen (picrosirius red). We found (1) increased coronary arteriolar staining with pFN antibody on day 2, with an increasing number of vessels involved over 14 days; (2) pFN appearing first in the media and adventitia and subsequently the interstitial space; (3) fibroblast proliferation on days 2 and 4, and enhanced expression of type I collagen mRNA in these adventitial and interstitial cells on days 4 and 7; (4) accumulation of macrophages in the adventitia of involved vessels during the period of observation; and (5) a perivascular fibrosis of involved vessels on day 14.(ABSTRACT TRUNCATED AT 250 WORDS)
Ratajska
A
A
Department of Internal Medicine, University of Missouri Health Sciences Center, Columbia 65212.
Campbell
S E
SE
Cleutjens
J P
JP
Weber
K T
KT
D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003331:Coronary Vessels / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D005353:Fibronectins / Q000032:analysis / Q000097:blood / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008954:Models, Biological; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005353:Fibronectins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D000804:Angiotensin II; D003094:Collagen