Tyrosine kinase inhibitors modulate agonist-induced vasodilation in the hamster cheek pouch

The purpose of this study was to determine whether inhibitors of tyrosine k inase attenuate vasodilation elicited by endogenously elaborated and exogen ously applied nitric oxide in the in situ peripheral microcirculation. Usin g intravital microscopy, we found that pretreatment with genistein (1.0 mu M) and tyrphostin 25 (10.0 mu M), two structurally unrelated tyrosine kinas e inhibitors, significantly attenuated acetylcholine-, bradykinin- and nitr oglycerin-induced dilation of second-order arterioles (51 +/- 1 mu m) in th e in situ hamster cheek pouch (P < 0.05). Both inhibitors nearly abrogated acetylcholine-induced responses but only partially blocked bradykinin- and nitroglycerin-induced vasodilation. Genistein and tyrphostin 25 alone had n o significant effects on resting arteriolar diameter and on adenosine-induc ed vasodilation in the cheek pouch. On balance, these data indicate that ty rosine kinase inhibitors attenuate endogenously elaborated and exogenously applied nitric oxide-induced vasodilation in the in situ hamster cheek pouc h. However, the extent of tyrosine kinase inhibitor-sensitive pathway invol vement in this response appears to be agonist dependent.