Role of tyrosine kinase in erythrocyte lysate-induced contraction in rabbit cerebral arteries

Object. This study was undertaken to explore whether erythrocyte lysate, a proposed cause of vasospasm, produces vasoconstriction by activation of tyrosine kinase in rabbit cerebral arteries. Methods. Isometric tension was used to monitor contractions in rabbit basilar arteries induced by erythrocyte lysate, 5-hydroxytryptamine (5-HT), or KCl in the absence or presence of tyrosine kinase inhibitors. Erythrocyte lysate, 5-HT, or KCl produced concentration-dependent contractions in rabbit basilar arteries. Preincubation with the tyrosine kinase inhibitors tyrphostin A23 and genistein (30 and 100 μM), but not diadzein, an inactive analog of genistein, attenuated significantly the contraction induced by erythrocyte lysate (p < 0.05). Tyrphostin A23, genistein, and diadzein (30 μM) failed to reduce the contraction caused by 5-HT. Genistein, but not tyrphostin A23 or diadzein (30 μM), attenuated significantly the contraction induced by KCl (p < 0.05). In another series, arterial rings were initially contracted with erythrocyte lysate, 5-HT, or KCl and the relaxant effect of genistein was then tested. Genistein relaxed rabbit basilar arteries that had been contracted by exposure to erythrocyte lysate, 5-HT, or KCl (30-100 μM; p < 0.05). Conclusions. These data indicate that tyrosine kinase may play a role in the regulation of cerebral arterial contraction and tyrosine kinase inhibitors may be useful in the management of cerebral vasospasm.