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The present study was designed to investigate the influence of hypertension and of long-term treatment with the dihydropyridine calcium antagonist isradipine on the morphology of the femoral artery in spontaneously hypertensive rats (SHR).Systolic blood pressure (SBP), body weight and morphology of the femoral artery were evaluated, and the ultrastructure of the endothelium was analysed by transmission and scanning electron microscopy.SHR were divided into three groups, a control group which was left untreated and two isradipine treatment groups, one at 0.01 mg/kg per day and the other at 0.1 mg/kg per day. Two age-matched groups of Wistar–Kyoto (WKY) rats were included in the study; one group was left untreated and was used as a normotensive reference group and the other was treated with isradipine at 0.1 mg/kg per day. The study lasted 12 weeks.SBP did not change in the WKY rats, whether treated with isradipine or not, but was significantly increased in SHR as a function of age. The lower dose of isradipine did not alter SBP in the SHR, but the higher dose brought SBP values into the normal range after the first week of treatment.Light microscopy of sections of the femoral artery did not reveal any structural differences in the five rat groups examined. Both transmission and scanning electron microscopy showed endothelial alterations in the SHR, together with thickening of the internal elastic lamina. Treatment with isradipine significantly improved the morphology of the endothelium in SHR. The higher dose was more effective, but the lower dose partly countered the hypertension-dependent changes in the morphology of the endothelium. No significant modifications to the structure of the endothelium were noticed in isradipine-treated WKY rats compared with untreated WKY rats.The results show that structural changes occur in the endothelium of the femoral artery of SHR and that isradipine treatment has a protective effect. This protective effect is probably only partly dependent on the antihypertensive properties of the compound.