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 cer ebral artery preparations contracted with oxyhemoglobin and phorbol myrista te acetate with the IC50 values 0.66 +/- 0.1 and 1.1 +/- 0.1 mu M, respecti vely. In cerebrovascular smooth muscle cells, oxyhemoglobin and phorbol myr istate acetate induced protein kinase C activation, which was 220 +/- 7% an d 203 +/- 8% of control, respectively. The increase in protein kinase C act ivity was prevented by tamoxifen. The results suggest that the ability of t amoxifen to reverse vasoconstriction is mediated, at least in part, via inh ibition of protein kinase C. (C) 2000 Elsevier Science B.V. All rights rese rved.