Restoration of vasodilation and CBF autoregulation by genistein in rat pial artery after brain injury

This study determined whether, after fluid percussion injury (FPI), tyrosin e kinase activation is coupled to inhibition of K+ channels and alteration in cerebral blood flow (CBF) autoregulation in the rat pial artery. Injury of moderate severity (2-2.5 atm) was produced by FPI in anesthetized rats e quipped with a closed cranial window. The suppressed vasodilation of the pi al arterioles to calcitonin gene-related peptide (CGRP) and levcromakalim ( LMK) and altered lower limit of CBF autoregulation after FPI were restored by genistein but not by daidzein, an inactive analog. Vasodilation to S-nit roso-N-acetyl penicillamine (0.1-10 mu mol/l) was, however, little influenc ed after FPI. The restored vasodilation was decreased by sodium orthovanada te, suggesting the reciprocal action of tyrosine phosphorylation and dephos phorylation. After FPI, CGRP-induced vasodilation restored by genistein (10 mu mol/l) was strongly antagonized by iberiotoxin but not by glibenclamide , whereas LMK-induced vasodilation was, in contrast, inhibited by glibencla mide but not by iberiotoxin. Taken together, we suggest that, after FPI, ac tivation of tyrosine kinase links the inhibition of K+ channels to impaired autoregulatory vasodilation in response to acute hypotension and alteratio n in CBF autoregulation in the rat pial artery.