title: Treatment with nicardipine protects brain in an animal model of hypertension-induced damage.
abstract: Control of blood pressure protects from the development of cerebrovascular lesions and vascular dementia (VaD). This study has assessed the influence of treatment with the dihydropyridine-type Ca2+ antagonist nicardipine on brain microanatomical changes in spontaneously hypertensive rats (SHR). SHR were treated from 16th to 26th week of age with hypotensive (3 mg/Kg/day) or non-hypotensive (0.1 mg/Kg/day) doses of nicardipine, with the non-dihydropyridine-type vasodilator hydralazine (10 mg/kg/day) or with vehicle (control group). Untreated age-matched Wistar Kyoto (WKY) rats were used as a normotensive reference group. Brain volume, number of neurons, glial fibrillary-acidic protein (GFAP)-immunoreactive astrocytes and neurofilament 200 KDa (NFP)-immunoreactivity (IR) were assessed in frontal and occipital cortex, hippocampus and striatum. A decrease of volume and number of nerve cells and a loss of NFP-IR was found in the frontal and occipital cortex and in the CA1 subfield of hippocampus and in the striatum of SHR. Treatment with nicardipine countered microanatomical changes occurring in SHR, whereas hydralazine displayed a less pronounced effect. Comparatively, the non-hypotensive dose of nicardipine was less active than the hypotensive one. The observation that equihypotensive doses of nicardipine or hydralazine did not protect brain in the same way from hypertensive brain damage suggests that lowering blood pressure is per se not enough for affording neuroprotection. The demonstration of neuroprotective effect of nicardipine suggests an use of the compound in situations in which hypertension is accompanied by the risk of brain damage.
authors.affiliation: Sezione di Anatomia Umana, Dipartimento di Scienze Farmacologiche e Medicina Sperimentale, Università di Camerino, Camerino, Italy. francesco.amenta@unicam.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Amenta
authors.forename: Daniele
authors.initials: D
authors.lastname: Tomassoni
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D000959:Antihypertensive Agents; D018696:Neuroprotective Agents; D009529:Nicardipine