TY - JOUR
T1 - Hypoxic dilatation of porcine small coronary arteries
T2 - Role of endothelium and K(ATP)-channels
AU - Liu, Qiang
AU - Flavahan, Nicholas A.
PY - 1997
Y1 - 1997
N2 - 1. The aim of the present study was to determine the cellular mechanims and potential mediators involved in hypoxic dilatation of porcine small coronary arteries. 2. Small coronary arteries were isolated from a branch of the left anterior descending artery of porcine hearts, cannulated with glass micropipettes and studied in a perfusion myograph system. At a transmural pressure of 40 mmHg, the arteries had an internal diameter of 167.8 ± 6.6 μm (n = 37). 3. In arteries contracted with acetylcholine (ACh), hypoxia (0% O2, 30 min) caused dilatation (86.9 ± 6.7% relaxation, n = 6) in vessels with endothelium but constriction in endothelium-denuded vessels. 4. Hypoxic vasodilatation occurring in arteries with endothelium was abolished by the K(ATP) channel inhibitor, glibenclamide (0.44 μM), but was not affected by inhibition of nitric oxide synthase (L-NAME, 44 μM) or cyclo-oxygenase (indomethacin, 4.4 μM). 5. Bradykinin evoked endothelium-dependent relaxation that was inhibited by L-NAME (44 μM) but not glibenclamide 0.44 μM). Cromakalim (0.1-0.3 μM), a K(ATP) channel opener, caused relaxation that was inhibited by glibenclamide, but was not affected by L-NAME (44 μM) and/or indomethacin (4.4 μM). 6. Endothelium-removal inhibited vasodilatation evoked by cromakalim, but increased vasodilator responses to the NO donor, SIN-1 (10-8 to 10-5 M). 7. These results indicate that hypoxia acted directly on vascular smooth muscle of small coronary arteries to cause contraction. However, this effect was overwhelmed by endothelium-dependent relaxation in response to hypoxia. This relaxation was most likely mediated by release of an endothelium-derived factor, distinct from nitric oxide or prostacyclin, that activated smooth muscle K(ATP)-channels.
AB - 1. The aim of the present study was to determine the cellular mechanims and potential mediators involved in hypoxic dilatation of porcine small coronary arteries. 2. Small coronary arteries were isolated from a branch of the left anterior descending artery of porcine hearts, cannulated with glass micropipettes and studied in a perfusion myograph system. At a transmural pressure of 40 mmHg, the arteries had an internal diameter of 167.8 ± 6.6 μm (n = 37). 3. In arteries contracted with acetylcholine (ACh), hypoxia (0% O2, 30 min) caused dilatation (86.9 ± 6.7% relaxation, n = 6) in vessels with endothelium but constriction in endothelium-denuded vessels. 4. Hypoxic vasodilatation occurring in arteries with endothelium was abolished by the K(ATP) channel inhibitor, glibenclamide (0.44 μM), but was not affected by inhibition of nitric oxide synthase (L-NAME, 44 μM) or cyclo-oxygenase (indomethacin, 4.4 μM). 5. Bradykinin evoked endothelium-dependent relaxation that was inhibited by L-NAME (44 μM) but not glibenclamide 0.44 μM). Cromakalim (0.1-0.3 μM), a K(ATP) channel opener, caused relaxation that was inhibited by glibenclamide, but was not affected by L-NAME (44 μM) and/or indomethacin (4.4 μM). 6. Endothelium-removal inhibited vasodilatation evoked by cromakalim, but increased vasodilator responses to the NO donor, SIN-1 (10-8 to 10-5 M). 7. These results indicate that hypoxia acted directly on vascular smooth muscle of small coronary arteries to cause contraction. However, this effect was overwhelmed by endothelium-dependent relaxation in response to hypoxia. This relaxation was most likely mediated by release of an endothelium-derived factor, distinct from nitric oxide or prostacyclin, that activated smooth muscle K(ATP)-channels.
KW - Arteriole
KW - Microcirculation
KW - Nitric oxide
KW - Vascular smooth muscle
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U2 - 10.1038/sj.bjp.0700939
DO - 10.1038/sj.bjp.0700939
M3 - Article
C2 - 9051315
AN - SCOPUS:0031039701
SN - 0007-1188
VL - 120
SP - 728
EP - 734
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 4
ER -