Acute hypoxia induces vasodilation and increases coronary blood flow by activating inward rectifier K(+) channels.
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.
Park
Won Sun
WS
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.
Son
Youn Kyoung
YK
Kim
Nari
N
Ko
Jae-Hong
JH
Kang
Sung Hyun
SH
Warda
Mohamad
M
Earm
Yung E
YE
Jung
In Duk
ID
Park
Yeong-Min
YM
Han
Jin
J
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*
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