EFFECT OF LONG-TERM TREATMENT WITH THE DIHYDROPYRIDINE-TYPE CALCIUM-CHANNEL BLOCKER DARODIPINE (PY-108-068) ON THE CEREBRAL CAPILLARY NETWORK IN AGED RATS

The effects of treatment with the dihydropyridine Ca+2 antagonist daro dipine (PY 108-068) on age-related changes in the cerebral capillary n etwork was studied using alkaline phosphatase histochemistry with quan titative image analysis. The investigation was performed on male Wista r rats of 12 months (adult reference group) and 27 months. The 27-mont h-old rats consisted of two groups, the first of control untreated ani mals and the second of rats receiving an oral dose of 5 mg/kg/day of d arodipine from the 21st to the 27th month. The cerebral areas examined included the frontal cortex, the occipital cortex, Ammon's horn of th e hippocampus, and the dentate gyrus, The number and the average lengt h of alkaline phosphatase-positive capillaries were decreased in old r ats, when compared with adult rats. The intercapillary distance, which is considered as a sensitive parameter for capillary density was incr eased in aged rats in comparison to adult rats. The capillary diameter was increased slightly or unchanged in old rats, The Ammon's horn and the frontal cortex were the cerebral areas most affected by age-depen dent changes of the capillary network. Treatment with darodipine incre ased the number and the average length of alkaline phosphatase-reactiv e capillaries and reduced the intercapillary distance and the diameter of cerebral capillaries in old rats. The pericapillary microrenvironm ent of the Ammon's horn was the most sensitive to treatment with darod ipine. The above results showed that treatment with darodipine is capa ble of counteracting some microvascular changes occurring in the brain of aged rats. This suggests that the blockade of dihydropyridine-type Ca2+ channels has a positive effect on the brain microvascular system and may counteract the impairment of pericapillary microenvironment o ccurring with aging.