title: Left ventricular fibrosis in renovascular hypertensive rats. Effect of losartan and spironolactone.
abstract: Myocardial fibrosis resulting from arterial hypertension alters myocardial structure and function. Myocardial fibrosis is characterized by a pathological accumulation of types I and III collagens. We used an aldosterone antagonist (spironolactone) and an angiotensin II antagonist (losartan) to elucidate the respective role of these hormones and hypertension in the development of myocardial fibrosis in the Goldblatt model of two-kidney, one clip hypertension in the rat. Fibrosis was assessed by computer-assisted morphometry in the interstitial space, around coronary arteries, in microscar areas, and on left ventricular sections stained with Sirius red and by biochemical techniques. Morphometry was performed with both standard light and polarization microscopy; this latter method was used to quantify yellow-red and green collagen fibers. Concurrently, type I and type III collagen mRNAs were evaluated by a semiquantitative polymerase chain reaction method. The collagen content of the untreated two-kidney, one clip hypertensive rats increased mainly around the coronary arteries; the number and surface area of microscars also increased in chronic hypertension. Losartan treatment decreased systolic pressure and yellow-red collagen fiber content in all areas, whereas spironolactone treatment decreased green collagen fiber content without decreasing systolic pressure. mRNA levels for types I and III collagens showed profiles similar to those of yellow-red and green collagen fiber contents, respectively, suggesting that yellow-red collagen fibers are mainly type I collagen fibers and green collagen fibers are mainly type III collagen fibers. These results suggest that angiotensin II, possibly together with hypertension, and aldosterone, independently of hypertension, have a major influence on myocardial fibrosis, inducing type I and type III collagen deposits, respectively, mainly around coronary arteries.
authors.affiliation: Unité 430 INSERM, Hôpital Broussais, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Nicoletti
authors.forename: D
authors.initials: D
authors.lastname: Heudes
authors.forename: N
authors.initials: N
authors.lastname: Hinglais
authors.forename: M D
authors.initials: MD
authors.lastname: Appay
authors.forename: M
authors.initials: M
authors.lastname: Philippe
authors.forename: C
authors.initials: C
authors.lastname: Sassy-Prigent
authors.forename: J
authors.initials: J
authors.lastname: Bariety
authors.forename: J B
authors.initials: JB
authors.lastname: Michel
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001669:Biochemical Phenomena; D001671:Biochemistry; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004719:Endomyocardial Fibrosis / Q000209:etiology / Q000473:pathology; D005355:Fibrosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D019808:Losartan; D008859:Microscopy, Polarization; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000494:pharmacology* / Q000627:therapeutic use; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D012333:RNA, Messenger; D013777:Tetrazoles; D000804:Angiotensin II; D013148:Spironolactone; D003094:Collagen; D019808:Losartan