ARTERIAL SMOOTH-MUSCLE CELL PHENOTYPE IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

The aim of this study was to determine the phenotype of smooth muscle cells in the arteries of chronically hypertensive animals and to analy ze the effects of treatments known to increase the survival of the ani mal without a clear effect on its hypertensive state. Stroke-prone spo ntaneously hypertensive rats (SHRSP) kept on a 1% sodium drinking solu tion 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 fib ronectin, alpha-smooth muscle actin, and nonmuscle myosin. We demonstr ated that phenotypes of smooth muscle cells of the SHRSP differ from t hose found in Wistar-Kyoto rats. The difference in phenotype is specif ic for the vessel type: ie, an increased expression of nonmuscle myosi n in the aorta and of both EIIIA fibronectin and nonmuscle myosin in t he coronary arteries. The two diuretics (1) had no effect on blood pre ssure, (2) prevented or did not prevent the increase in medial thickne ss, and (3) prevented changes in both smooth muscle cell phenotype and ischemic tissular lesions. Taken together, the results suggest that i n SHRSP the changes in the phenotype of smooth muscle cells and the th ickness of arteries are unrelated events. We propose that the maintena nce of the contractile phenotype of the arterial smooth muscle cells c ould be an essential parameter involved in the prevention of the delet erious consequences characteristic of a severe hypertensive state.