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(Hypertension. 2001;37:e4.)
© 2001 American Heart Association, Inc.

Hypertension Electronic Pages

Differential Effect of Chronic Antihypertensive Treatment on Vascular Smooth Muscle Cell Phenotype in Spontaneously Hypertensive Rats

Rosario Bravo; Beatriz Somoza; Mariano Ruiz-Gayo; Carmen González; Luis Miguel Ruilope; Maria Soledad Fernández-Alfonso

From the Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid (R.B., B.S., M.S.F.-A); the Departamento de Ciencias Biomédicas I, Facultad de Ciencias Técnicas Experimentales, Universidad San Pablo CEU (M.R.-G.); the Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid (C.G.); and the Servicio de Nefrología, Unidad de Hipertensión, Hospital 12 de Octubre (L.M.R.), Madrid, Spain.

Correspondence to Maria S. Fernández-Alfonso, Departamento de Farmacología, Facultad de Farmacia, Plaza de Ramón y Cajal, sn, 28040 Madrid, Spain. E-mail marisolf{at}eucmos.sim.ucm.es

Abstract—The aim of this study was to investigate the effect of chronic losartan or captopril on vascular smooth muscle cell (VSMC) phenotype and vascular function in spontaneously hypertensive rats. Male 12-week-old rats were treated for 16 weeks with losartan (15 mg/kg per day) or captopril (60 mg/kg per day) in their drinking water. Systolic blood pressure, measured by the tail-cuff method, was reduced 40 mm Hg in both treatment groups compared with a nontreated control group. Cell structure and proliferation studies were performed in VSMCs obtained from rat carotid arteries. Cells from the losartan-treated group showed a significant reduction in size, total protein content, and nucleus number, as well as proliferation after stimulation with 10% fetal calf serum and an increased percentage of cells in the G₁ phase compared with the control and captopril-treated groups. Functional studies were performed in isolated carotid arteries from these groups. Contractions elicited by 75 mmol/L KCl or 10^-7 mol/L norepinephrine and relaxations elicited by acetylcholine were similar in all groups. Concentration-response curves to angiotensin I or angiotensin II (10^-10 to 3x10^-7 mol/L) were almost abolished in the losartan-treated group and were not modified by preincubation with the angiotensin type 2 receptor antagonist PD 123,319. These results suggest that long-term losartan treatment significantly changes VSMC phenotype and proliferative status, apparently unrelated to blood pressure lowering or to endothelial function improvements.

Key Words: losartan • captopril • muscle, smooth, vascular • cell cycle • hypertrophy

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