Role of tyrosine kinase in erythrocyte lysate-induced contraction in rabbit cerebral arteries.
OBJECTIVE
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 microM), 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 microM) failed to reduce the contraction caused by 5-HT. Genistein, but not tyrphostin A23 or diadzein (30 microM), 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 microM; 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.
Department of Neurosurgery, Institute for Medical Sciences, Chonbuk National University, Chonju, Korea. kcj@moak.chonbuk.ac.kr
C J
CJ
Kim
K W
KW
Kim
J W
JW
Park
J C
JC
Lee
J H
JH
Zhang
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology*; D002396:Catechols / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000502:physiology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005260:Female; D019833:Genistein / Q000494:pharmacology; D002546:Ischemic Attack, Transient / Q000209:etiology; D007529:Isoflavones / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D013347:Subcellular Fractions / Q000502:physiology*; D020032:Tyrphostins; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D002396:Catechols; D004791:Enzyme Inhibitors; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D009570:Nitriles; D020032:Tyrphostins; D014665:Vasodilator Agents; D012701:Serotonin; C004742:daidzein; D011189:Potassium Chloride; D019833:Genistein; D011505:Protein-Tyrosine Kinases; C060641:tyrphostin A23