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Sulfonylurea receptor‐dependent and ‐independent pathways for K ATP channel opener‐mediated vasodilation
Author(s) -
Adebiyi Adebowale,
McNally Elizabeth M,
Jaggar Jonathan H
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.965.7
Subject(s) - diazoxide , pinacidil , mesenteric arteries , vasodilation , sulfonylurea receptor , chemistry , ryanodine receptor , iberiotoxin , medicine , endocrinology , glibenclamide , pharmacology , receptor , artery , insulin , diabetes mellitus
K ATP channel openers, including diazoxide and pinacidil, activate both plasma membrane and mitochondrial K ATP channels. Here, we investigated functional molecular targets for diazoxide and pinacidil in myocytes of murine resistance‐size mesenteric arteries. In pressurized (60 mmHg) arteries, ryanodine, a Ca 2+ spark inhibitor, iberiotoxin, a K Ca channel blocker, 4‐AP, a K v channel blocker, MnTMPyP, an antioxidant, and ryanodine+4‐AP reduced diazoxide‐induced dilations by between 45 and 77%, but did not alter pinacidil‐induced dilations. RT‐PCR indicated that isolated mesenteric artery myocytes expressed sulfonylurea receptors (SUR) 2A and 2B, but did not express SUR1. Pinacidil‐induced dilation in arteries of SUR2‐deficient (SUR2 −/− ) mice was ∼10% of that in wild‐type control arteries, whereas diazoxide‐induced dilation was similar in SUR2 −/− and wild‐type. Atpenin, a specific mitochondrial ETC complex II (ETC II ) inhibitor, dilated arteries similarly to diazoxide and this effect was attenuated by MnTMPyP and ryanodine+4‐AP. Atpenin also reduced diazoxide‐induced dilation, but did not alter pinacidil‐induced dilation. Data indicate that pinacidil‐induced vasodilation requires SUR2. In contrast, diazoxide‐induced vasodilation does not require SURs and is mediated by ETC II inhibition, a ROS elevation, and Ca 2+ spark, K Ca channel, and K v channel activation. NIH/AHA