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 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 approximately 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 G(1) 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.
Bravo
R
R
Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid.
Somoza
B
B
Ruiz-Gayo
M
M
González
C
C
Ruilope
L M
LM
Fernández-Alfonso
M S
MS
D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects; D006973:Hypertension / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy; D019808:Losartan / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010641:Phenotype; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000187:drug effects
D000959:Antihypertensive Agents; D002216:Captopril; D019808:Losartan