Open AccessContributions of K ATP and K Ca channels to cerebral arteriolar dilation to hypercapnia in neonatal brain
Author(s) -
Nnorom Chukwuma C.,
Davis Corinne,
Fedinec Alexander L.,
Howell Khadesia,
Jaggar Jonathan H.,
Parfenova Helena,
Pourcyrous Massroor,
Leffler Charles W.
Publication year - 2014
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12127
Subject(s) - glibenclamide , hypercapnia , pinacidil , potassium channel , dilator , anesthesia , iberiotoxin , medicine , pharmacology , chemistry , cardiology , endocrinology , acidosis , diabetes mellitus
Mechanisms by which Pco 2 controls cerebral vascular tone remain uncertain. We hypothesize that potassium channel activation contributes to the neonatal cerebrovascular dilation in response to increases in Pa co 2 . To test this hypothesis, experiments were performed on newborn pigs with surgically implanted, closed cranial windows. Hypercapnia was induced by ventilation with elevated Pco 2 gas in the absence and presence of the K ATP channel inhibitor, glibenclamide and/or the K Ca channel inhibitor, paxillin. Dilations to pinacidil, a selective K ATP channel activator, without and with glibenclamide, were used to evaluate the efficacy of K ATP channel inhibition. Dilations to NS1619, a selective K Ca channel activator, without and with paxillin, were used to evaluate the efficacy of K Ca channel inhibition. Cerebrovascular responses to the K ATP and K Ca channel activators, pinacidil and NS1619, respectively, cAMP ‐dependent dilator, isoproterenol, and cGMP ‐dependent dilator, sodium nitroprusside ( SNP ), were used to evaluate the selectivity of glibenclamide and paxillin. Glibenclamide blocked dilation to pinacidil, but did not inhibit dilations to NS1619, isoproterenol, or SNP. Glibenclamide prior to hypercapnia decreased mean pial arteriole dilation ~60%. Glibenclamide treatment during hypercapnia constricted arterioles ~35%. The level of hypercapnia, Pa co 2 between 50 and 75 mmHg, did not appear to be involved in efficacy of glibenclamide in blocking dilation to Pa co 2 . Similarly to glibenclamide and K ATP channel inhibition, paxillin blocked dilation to the K Ca channel agonist, NS1619, and attenuated, but did not block, arteriolar dilation to hypercapnia. Treatment with both glibenclamide and paxillin abolished dilation to hypercapnia. Therefore, either glibenclamide or paxillin that block dilation to their channel agonists, pinacidil or NS1619, respectively, only partially inhibit dilation to hypercapnia. Block of both K ATP and K Ca channels completely prevent dilation hypercapnia. These data suggest hypercapnia activates both K ATP and K Ca channels leading to cerebral arteriolar dilation in newborn pigs.