title: Acute hypoxia induces vasodilation and increases coronary blood flow by activating inward rectifier K(+) channels.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, College of Medicine, Cardiovascular and Metabolic Disease Research Center, Biohealth Products Research Center, Inje University, 633-165 Gaegeum-Dong, Busanjin-Gu, Busan, 613-735, South Korea.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Son
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Ko
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Kang
authors.forename: Mohamad
authors.initials: M
authors.lastname: Warda
authors.forename: Yung E
authors.initials: YE
authors.lastname: Earm
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000208:Acute Disease; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002227:Carbazoles / Q000494:pharmacology; D003326:Coronary Circulation / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology; D013873:Thionucleotides; D014664:Vasodilation / Q000502:physiology*
chemical_list: D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D011758:Pyrroles; D013873:Thionucleotides; C083763:8-bromoguanosino-3',5'-cyclic monophosphorothioate; C017759:9-(tetrahydro-2-furyl)-adenine; C057416:KT 5720; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D000225:Adenine; D005905:Glyburide