title: Arterial smooth muscle cell phenotype in stroke-prone spontaneously hypertensive rats.
abstract: The aim of this study was to determine the phenotype of smooth muscle cells in the arteries of chronically hypertensive animals and to analyze the effects of treatments known to increase the survival of the animal without a clear effect on its hypertensive state. Stroke-prone spontaneously hypertensive rats (SHRSP) kept on a 1% sodium drinking solution were untreated or treated with one of two diuretics, indapamide (3 mg/kg per day) or hydrochlorothiazide (20 mg/kg per day), from 6 to 13 weeks of age. Phenotype was characterized by the immunolabeling of arteries with antibodies raised against a cellular form (EIIIA) of fibronectin, alpha-smooth muscle actin, and nonmuscle myosin. We demonstrated that phenotypes of smooth muscle cells of the SHRSP differ from those found in Wistar-Kyoto rats. The difference in phenotype is specific for the vessel type: ie, an increased expression of nonmuscle myosin in the aorta and of both EIIIA fibronectin and nonmuscle myosin in the coronary arteries. The two diuretics (1) had no effect on blood pressure, (2) prevented or did not prevent the increase in medial thickness, and (3) prevented changes in both smooth muscle cell phenotype and ischemic tissular lesions. Taken together, the results suggest that in SHRSP the changes in the phenotype of smooth muscle cells and the thickness of arteries are unrelated events. We propose that the maintenance of the contractile phenotype of the arterial smooth muscle cells could be an essential parameter involved in the prevention of the deleterious consequences characteristic of a severe hypertensive state.
authors.affiliation: U127 INSERM, Hôpital Lariboisière, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Contard
authors.forename: A
authors.initials: A
authors.lastname: Sabri
authors.forename: M
authors.initials: M
authors.lastname: Glukhova
authors.forename: S
authors.initials: S
authors.lastname: Sartore
authors.forename: F
authors.initials: F
authors.lastname: Marotte
authors.forename: J P
authors.initials: JP
authors.lastname: Pomies
authors.forename: P
authors.initials: P
authors.lastname: Schiavi
authors.forename: D
authors.initials: D
authors.lastname: Guez
authors.forename: J L
authors.initials: JL
authors.lastname: Samuel
authors.forename: L
authors.initials: L
authors.lastname: Rappaport
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000503:physiopathology; D005353:Fibronectins / Q000032:analysis; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D007190:Indapamide / Q000494:pharmacology*; D007672:Kidney Cortex / Q000187:drug effects / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009218:Myosins / Q000096:biosynthesis*; D009336:Necrosis; D010641:Phenotype; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY / Q000502:physiology; D012982:Sodium, Dietary / Q000494:pharmacology
chemical_list: D000199:Actins; D005353:Fibronectins; D012982:Sodium, Dietary; D006852:Hydrochlorothiazide; D009218:Myosins; D007190:Indapamide