Effect of calcium antagonists on regional cerebral blood flow in transplanted rat brain tumors.
We studied the effect of intracarotid infusion of various calcium antagonists on regional CBF (rCBF) in the C6 rat glioma by a hydrogen clearance method. Nimodipine at doses of 0.1, 0.5 and 1 microgram/kg/min was found to produce tumor-specific increases in the rCBF (40.2 +/- 18.4%, p < 0.01, 67.8 +/- 32.6%, p < 0.001 and 37.3 +/- 37.2%, p < 0.05, respectively) without affecting systemic blood pressure. Regarding the time course of the nimodipine effects, at a dose of 0.5 micrograms/kg/min, rCBF in the tumor showed maximum value at fifteen minutes after the start of the intracarotid infusion. Diltiazem at doses of 5, 20, and 40 micrograms/kg/min also increased tumor rCBF in a dose-dependent manner (27.9 +/- 12.5%, p < 0.001, 52.0 +/- 21.8%, p-AN 0.001 and 54.5 +/- 18.4%, p < 0.001, respectively). Both nifedipine and flunarizine significantly increased the rCBF in the tumor, while they did not cause a higher percent increase of the rCBF when compared with those of nimodipine and diltiazem. No significant percent increase of the rCBF in the tumor was observed in verapamil treated rats. These results indicate that tumor vessels may have an altered response to calcium antagonists, especially to nimodipine and diltiazem, when compared to normal brain capillaries. The varied responses to calcium antagonists could be explained by their differences in tissue selectivity and affinity to calcium channels.
Matsukado
K
K
Department of Neurosurgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Ikezaki
K
K
Nomura
T
T
Fukui
M
M
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D005444:Flunarizine / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D009368:Neoplasm Transplantation; D009543:Nifedipine / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D009553:Nimodipine; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D005444:Flunarizine