Hypertensive brain damage: comparative evaluation of protective effect of treatment with dihydropyridine derivatives in spontaneously hypertensive rats.

Hypertension is the main risk factor for cerebrovascular disease including vascular dementia and control of blood pressure might protect from lesions causing cognitive impairment. The influence of anti-hypertensive treatment on hypertensive brain damage was assessed in spontaneously hypertensive rats (SHR). SHR and age-matched normotensive Wistar Kyoto (WKY) rats were treated from the 14-26th week of age with the dihydropyridine-type Ca2+ channel blockers lercanidipine, manidipine and nimodipine and as a reference with the non-dihydropyridine-type vasodilator hydralazine. Volume of brain areas, number of nerve cells and glial fibrillary-acidic protein (GFAP)-immunoreactive astrocytes and neurofilament 200 kDa immunoreactivity were investigated in frontal and occipital cortex and in hippocampus. In control SHR, systolic blood pressure (SBP) was significantly higher in comparison with WKY rats. Compounds tested decreased to a similar extent SBP values in SHR, with the exception of nimodipine that caused a smaller reduction of SBP compared with other compounds. Decreased volume and number of nerve cells and loss of neurofilament protein immunoreactivity were observed in SHR. GFAP-immunoreactive astrocytes increased in number (hyperplasia) and in size (hypertrophy) in the frontal and occipital cortex of control SHR, and only in number in the hippocampus. Anti-hypertensive treatment countered in part microanatomical changes occurring in SHR. Drugs investigated with the exception of nimodipine exerted an equi-hypotensive effect. In spite of this the best protection was exerted by lercanidipine and, to a lesser extent, by nimodipine. Compared with nimodipine, lercanidipine induced a more effective decrease of SBP. This may represent an advantage in the treatment of hypertension with risk of brain damage.