EFFECT OF LONG-TERM ISRADIPINE TREATMENT ON THE MORPHOLOGY OF THE ENDOTHELIUM IN THE AORTA OF SPONTANEOUSLY HYPERTENSIVE RATS

The influence of hypertension and of treatment with the dihydropyridine calcium channel blocker isradipine on the morphology of the thoracic aorta and of the aortic tunica intima were studied. Three experimental groups of male spontaneously hypertensive rats (SHR) of 10 weeks of age were used. Two groups were treated with a daily oral dose of 0.01 mg/Kg or of 0.1 mg/Kg of isradipine respectively. A third group of SHR was left untreated and served as control. Age-matched normotensive Wistar-Kyoto (WKY) rats were used as a reference group. Animals were allowed to survive for 12 weeks and were killed at 22 weeks of age. Systolic pressure values which did not change in WKY rats, significantly increased in SHR as a function of age. The dose of 0.1 mg/Kg/day isradipine reduced systolic pressure to normotensive values after the first week of treatment, whereas the lower one was ineffective. The area of the wall, the area of the tunica media and the wall-to-lumen ratio of the aorta significantly increased in SHR and decreased either with the antihypertensive and non-antihypertensive doses of isradipine. Transmission and scanning electron microscope analysis of the tunica intima revealed hypertrophy of the endothelial cells with an increase in sub endothelial space in SHR. An improvement of the endothelial morphology and a decrease in sub endothelial space was noticeable in isradipine-treated SHR. Although the hypotensive dose of the compound was the most effective, the non-hypotensive dose was active as well. The above results suggest that isradipine treatment may counter structural changes of the aorta of SHR and has a protective action on the hypertension-dependent modifications of the endothelium. The endothelial effects are probably dependent only in part by the hypotensive activity of the compound.