Vasopressin impairs K(ATP) and K(ca) channel function after brain injury.
This study was designed to characterize the role of vasopressin in impaired pial artery dilation to activators of the ATP sensitive K (K(ATP)) and calcium sensitive K (K(ca)) channel following fluid percussion brain injury (FPI) in newborn pigs equipped with a closed cranial window. Topical vasopressin was coadministered with the K(ATP) and K(ca) channel agonists cromakalim and NS1619 in a concentration approximating that observed in CSF following FPI. Vasopressin so administered attenuated pial artery dilation to these K(+) channel activators under conditions of equivalent baseline diameter during non injury conditions (13+/-1 and 23+/-1 vs. 4+/-1 and 10+/-2% for cromakalim 10(-8), 10(-6) M before and after vasopressin, respectively). Attenuated responses were fully restored when these agonists were coadministered with vasopressin and the vasopressin antagonist [l-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid) 2-(o-methyl)-Tyr-AVP] (MEAVP). Cromakalim and NS1619 induced pial artery dilation was attenuated following FPI and MEAVP preadministration partially prevented such impairment (13+/-1 and 23+/-1, sham control; 2+/-1 and 5+/-1, FPI; and 9+/-1 and 15+/-2%, FPI-MEAVP pretreated for responses to cromakalim 10(-8), 10(-6) M, respectively). These data show that vasopressin blunts K(ATP) and K(ca) channel mediated cerebrovasodilation. These data suggest that vasopressin contributes to impaired K(ATP) and K(ca) channel function after brain injury.
Salvucci
A
A
Department of Anesthesia, University of Pennsylvania, Philadelphia, PA 19104, USA.
Armstead
W M
WM
D000818:Animals; D000831:Animals, Newborn; D001562:Benzimidazoles / Q000494:pharmacology; D001930:Brain Injuries / Q000503:physiopathology*; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D002550:Cerebral Veins; D019806:Cromakalim / Q000494:pharmacology; D005260:Female; D008297:Male; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology*
D001562:Benzimidazoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019806:Cromakalim; D014667:Vasopressins; C086491:NS 1619