Differential effect of chronic antihypertensive treatment on vascular smooth muscle cell phenotype in spontaneously hypertensive rats

The aim of this study was to investigate the effect of chronic losartan or captopril on vascular smooth muscle cell (VSMC) phenotype and vascular func tion 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 d ay) in their drinking water. Systolic blood pressure, measured by the tail- cuff method, was reduced approximate to 40 mm Hg in both treatment groups c ompared with a nontreated control group. Cell structure and proliferation s tudies were performed in VSMCs obtained from rat carotid arteries. Cells fr om the losartan-treated group showed a significant reduction in size, total protein content, and nucleus number, as well as proliferation after stimul ation with 10% fetal calf serum and an increased percentage of cells in the G(1) phase compared with the control and captopril-treated groups. Functio nal studies were performed in isolated carotid arteries from these groups. Contractions elicited by 75 mmol/L KCI or 10(-7) mol/L norepinephrine and r elaxations elicited by acetylcholine were similar in all groups. Concentrat ion-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 mo dified by preincubation with the angiotensin type 2 receptor antagonist PD 123,319. These results suggest that long-term losartan treatment significan tly changes VSMC phenotype and proliferative status, apparently unrelated t o blood pressure lowering or to endothelial function improvements.