Acute hypoxia induces vasodilation and increases coronary blood flow by activating inward rectifier K(+) channels

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Park, Won Sun; Son, Youn Kyoung; Kim, Nari; Ko, Jae-Hong; Kang, Sung Hyun; Warda, Mohamad; Earm, Yung E.; Jung, In Duk; Park, Yeong-Min; Han, Jin
Issue Date
Pflugers Arch. 2007 Sep;454(6):1023-30. Epub 2007 May 8.
Acute DiseaseAdenine/analogs & derivatives/pharmacologyAnimalsAnoxia/*physiopathologyBlood Pressure/physiologyCarbazoles/pharmacologyCoronary Circulation/*physiologyCyclic AMP-Dependent Protein Kinases/antagonists & inhibitorsCyclic GMP/analogs & derivatives/pharmacologyCyclic GMP-Dependent Protein Kinases/antagonists & inhibitorsEnzyme Inhibitors/pharmacologyFemaleGlyburide/pharmacologyIndoles/pharmacologyMalePotassium Channel Blockers/pharmacologyPotassium Channels, Inwardly Rectifying/drug effects/*physiologyPyrroles/pharmacologyRabbitsSignal Transduction/physiologyVasodilation/*physiology
We examined the effects of acute hypoxia on vascular tone and coronary blood flow (CBF) in rabbit coronary arteries. In the pressurized arterial preparation of small arteries (<100 mum) and the Langendorff-perfused rabbit hearts, hypoxia induced coronary vasodilation and increased CBF in the presence of glibenclamide (K(ATP) channel blocker), Rp-8-Br-PET-cGMPs [cyclic guanosine monophosphate (cGMP)-dependent protein kinase inhibitor, Rp-cGMPs], and methionyl transfer RNA synthetase (MRS) 1334 (adenosine A(3) receptor inhibitor); these increases were inhibited by the inward rectifier K(+) (Kir) channel inhibitor, Ba(2+). These effects were blocked by the adenylyl cyclase inhibitor SQ 22536 and by the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) inhibitors Rp-8-CPT-cAMPs (Rp-cAMPs) and KT 5720. However, cGMP-dependent protein kinase was not involved in the hypoxia-induced increases of the vascular diameter and CBF. In summary, our results suggest that acute hypoxia can induce the opening of Kir channels in coronary artery that has small diameter (<100 mum) by activating the cAMP and PKA signalling pathway, which could contribute to vasodilation and, therefore, increased CBF.
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Physiology (생리학교실)Journal Papers (저널논문_생리학교실)
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