Effects of tamoxifen on oxyhemoglobin-induced cerebral vasoconstriction.
The effect of tamoxifen on oxyhemoglobin-mediated cerebral vasoconstriction was examined. Tamoxifen caused a concentration-dependent relaxation of cerebral artery preparations contracted with oxyhemoglobin and phorbol myristate acetate with the IC(50) values 0.66+/-0.1 and 1.1+/-0.1 microM, respectively. In cerebrovascular smooth muscle cells, oxyhemoglobin and phorbol myristate acetate induced protein kinase C activation, which was 220+/-7% and 203+/-8% of control, respectively. The increase in protein kinase C activity was prevented by tamoxifen. The results suggest that the ability of tamoxifen to reverse vasoconstriction is mediated, at least in part, via inhibition of protein kinase C.
Wickman
G
G
Department of Pharmacology, Faculty of Medicine and Dentistry, 9-70 Medical Sciences Building, University of Alberta, Edmonton, Alberta, Canada.
Vollrath
B
B
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010108:Oxyhemoglobins / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D013629:Tamoxifen / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D004965:Estrogen Antagonists; D010108:Oxyhemoglobins; D013629:Tamoxifen; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate