title: Vascular and neuronal hypertensive brain damage: protective effect of treatment with nicardipine.
abstract: OBJECTIVE
  The brain is sensitive to hypertension, which causes a variety of vascular and neuronal cerebral changes. The present study was designed to assess the effect of long-term treatment with the Ca2+ channel blocker nicardipine on intracerebral (intraparenchymal) arteries in spontaneously hypertensive rats (SHR) by using microanatomical techniques associated with image analysis. The effects of hypertension and treatment with nicardipine on nerve cells and glial fibrillary acid protein (GFAP)-immunoreactive glial cells were also evaluated.
  In SHR a significant increase in systolic blood pressure in comparison with age-matched normotensive Wistar-Kyoto (WKY) rats was noticeable. Treatment with nicardipine significantly reduced systolic pressure in the SHR. The media: lumen ratio and the thickness of the tunica media were increased in medium (diameter between 150 and 50 microns and small (diameter < 50 microns intracerebral arteries. This phenomenon was accompanied by luminal narrowing. Treatment with nicardipine significantly reduced the thickness of the tunica media, the media: lumen ratio and increased the luminal area, primarily at the level of small pial arteries and of intracerebral arteries.
  In control SHR, the number of neurones in the frontal and occipital cortex was reduced in comparison with normotensive WKY rats. GFAP-immunoreactive astrocytes were increased in number (hyperplasia) and in size (hypertrophy), both in the frontal cortex and in the occipital cortex of control SHR. In the CA1, field of the hippocampus, the number of neurones and their size were decreased in SHR in comparison with normotensive WKY rats. Hyperplasia of GFAP-immunoreactive astrocytes of white matter and hypertrophy of those of grey matter was also noticeable. No important changes were found in other portions of the hippocampus. Treatment with nicardipine increased the number of neurones in the frontal cortex and in the occipital cortex of SHR and countered hyperplasia and hypertrophy of GFAP-immunoreactive astrocytes. Moreover, it increased the number of neurones in the CA1 field of the hippocampus and decreased the number and the size of astrocytes of the white matter and grey matter, respectively.
  
  
  CONCLUSIONS
  These findings show that treatment of SHR with nicardipine significantly reduced systolic blood pressure and induced moderate vasodilation of both extracerebral and intracerebral arteries regulating cerebrovascular resistance. The compound also countered some microanatomical changes occurring in the hypertensive brain. The frontal and occipital (visual) cortex and the CA1 field of the hippocampus were the cerebral areas more sensitive to treatment with nicardipine. This suggests that nicardipine induces moderate cerebrovascular dilation and exerts neuroprotective effects on SHR neurones. The possible relevance of the neuroprotective actions of nicardipine in the hypertensive brain deserves to be evaluated in future studies.
authors.affiliation: Section on Human Anatomy, University of Camerino, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Amenta
authors.forename: P
authors.initials: P
authors.lastname: Strocchi
authors.forename: M
authors.initials: M
authors.lastname: Sabbatini
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000473:pathology; D001253:Astrocytes / Q000378:metabolism; D001925:Brain Damage, Chronic / Q000209:etiology / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009529:Nicardipine / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D002121:Calcium Channel Blockers; D005904:Glial Fibrillary Acidic Protein; D009529:Nicardipine