title: Restoration of vasodilation and CBF autoregulation by genistein in rat pial artery after brain injury.
abstract: This study determined whether, after fluid percussion injury (FPI), tyrosine 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 equipped with a closed cranial window. The suppressed vasodilation of the pial 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-nitroso-N-acetyl penicillamine (0.1--10 micromol/l) was, however, little influenced after FPI. The restored vasodilation was decreased by sodium orthovanadate, suggesting the reciprocal action of tyrosine phosphorylation and dephosphorylation. After FPI, CGRP-induced vasodilation restored by genistein (10 micromol/l) was strongly antagonized by iberiotoxin but not by glibenclamide, whereas LMK-induced vasodilation was, in contrast, inhibited by glibenclamide but not by iberiotoxin. Taken together, we suggest that, after FPI, activation of tyrosine kinase links the inhibition of K(+) channels to impaired autoregulatory vasodilation in response to acute hypotension and alteration in CBF autoregulation in the rat pial artery.
authors.affiliation: Department of Pharmacology, College of Medicine, Pusan National University, Pusan 602-739, Korea. hwhong@hyowon.pusan.ac.kr
authors.forename: K W
authors.initials: KW
authors.lastname: Hong
authors.forename: H K
authors.initials: HK
authors.lastname: Shin
authors.forename: C D
authors.initials: CD
authors.lastname: Kim
authors.forename: W S
authors.initials: WS
authors.lastname: Lee
authors.forename: B Y
authors.initials: BY
authors.lastname: Rhim
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D001930:Brain Injuries / Q000503:physiopathology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D019806:Cromakalim / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology*; D006706:Homeostasis; D008297:Male; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D026902:Potassium Channel Blockers; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D019806:Cromakalim; D026423:S-Nitroso-N-Acetylpenicillamine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases; D010396:Penicillamine; D015740:Calcitonin Gene-Related Peptide