Influence of treatment with the calcium channel blocker darodipine (PY 108-068) on the morphology of pial and coronary arteries in spontaneously hypertensive rats.

The present study was designed to assess the influence of treatment with the calcium channel blocker darodipine (PY 108-068) on the morphology of pial and coronary arteries in spontaneously hypertensive rats (SHR). Twelve week male SHR were used in this study. One group was treated with a daily dose of 5 mg/Kg of darodipine, while the control group of SHR was treated with placebo. Age-matched normotensive Wistar Kyoto (WKY) rats were used as a reference group. After 12 weeks of treatment the rats were sacrificed. The brains and the hearts were removed, embedded in resin, cut and used for light microscope analysis. Darodipine treatment reduced blood pressure in SHR. Morphometric analysis of different sized pial and coronary arteries revealed decreased arterial lumen in SHR in comparison with WKY rats. The area occupied by the tunica media and the media-to-lumen ratio were increased in SHR in comparison with WKY rats. In darodipine-treated rats the area occupied by the arterial lumen was increased in comparison with control SHR, whereas the area occupied by the tunica media and the media-to-lumen ratio were decreased. Pial arteries were more sensitive than coronary arteries to darodipine treatment. Medium and small sized pial and coronary arteries were most sensitive to darodipine treatment. Large-sized coronary artery branches were unaffected by pharmacological treatment. The above results suggest that treatment of SHR with darodipine is able to reduce high blood pressure and to counter the development of structural changes of pial and coronary arteries noticeable in SHR. The higher sensitivity of the cerebral vasculature to darodipine treatment is discussed.