The effect of Dotarizine--(Ca2+ channel blocker)--on vascular reactivity and ultrastructure of cerebral capillaries in animals subjected to anoxia.
Dotarizine--the novel piperazine derivative--belongs to wide spectrum Ca2+ channel antagonists. It was reported to have strong vasodilatatory and antiserotoninergic activities. Comparing with other Ca2+ channel blockers Dotarizine was found to have lower oral toxicity. In the present study the influence of the oral administration of the novel compound on the blood flow velocity changes in different cerebral arteries--in basilar artery (BA) and middle cerebral artery (MCA)--was investigated under hypoxic conditions. The ultrastructural morphological changes of intracerebral vessels endothelium in treated and untreated anoxic animal groups were also demonstrated. The experiments were carried out on rabbits. In the experimental group 25 mg/kg of Dotarizine dissolved in 0.25% agar was administered orally three times at the 10 hours' intervals. The sham group of animals was fed with agar of the same concentration. During anoxic conditions strong vasodilatory effects were observed in both investigated vessels of drug-treated animals. In the experimental group marked ultrastructural differences in parenchymal vessel endotheliumin comparison to sham group were revealed. Thus, the oral administration of Dotarizine might have effect on the various parts of the cerebrovascular system and can play significant role in improvement of various cerebrovascular disorders.
Kuridze
N
N
Department of Neurosurgery, Medical Research Centre, Polish Academy of Sciences, Warszawa.
Gajkowska
B
B
Czernicki
Z
Z
Jurkiewicz
J
J
Cervos-Navarro
J
J
D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology* / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use*; D002196:Capillaries / Q000187:drug effects / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000098:blood supply* / Q000187:drug effects*; D005260:Female; D002534:Hypoxia, Brain / Q000188:drug therapy*; D008297:Male; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use*; D011817:Rabbits
D001559:Benzhydryl Compounds; D002121:Calcium Channel Blockers; D010879:Piperazines; C083946:dotarizine