TY - JOUR
T1 - Pertussis toxin-sensitive G protein mediates coronary microvascular control during autoregulation and ischemia in canine heart
AU - Komaru, Tatsuya
AU - Wang, Yan
AU - Akai, Kenjiro
AU - Sato, Kouichi
AU - Sekiguchi, Nobuyo
AU - Sugimura, Akihiko
AU - Kumagai, Toshinobu
AU - Kanatsuka, Hiroshi
AU - Shirato, Kunio
PY - 1994/9
Y1 - 1994/9
N2 - GTP-binding regulatory proteins (G proteins) regulate various biological functions, but their participation in controlling coronary microvascular tone has not been established yet. The goal of the present study was to elucidate the role of pertussis toxin (PTX)-sensitive G protein in regulating coronary microvascular tone during autoregulation and ischemia. In 42 open-chest dogs, coronary arterial microvessels on the surface of the left ventricle were directly observed by epi-illuminated fluorescence microangiography using a floating objective system. PTX (300 ng/mL) was superfused onto the surface of the left ventricle for 2 hours to block G(i) and G(o) protein in epimyocardial coronary microvessels in vivo. PTX superfusion caused no change in the resting diameters of microvessels and significantly blocked the vasoconstriction induced by BHT 920 (a selective α2-agonist). After pretreatment with PTX or its vehicle, the left anterior descending coronary artery (LAD) was occluded by a hydraulic occluder to reduce coronary perfusion pressure (CPP) in a stepwise fashion. A mild stenosis (CPP, 60 mm Hg), a severe stenosis (CPP, .40 mm Hg), and complete occlusion were sequentially produced. Coronary flow velocity in the LAD distal to the stenotic site was continuously monitored. In both PTX and vehicle groups, flow velocity did not significantly decrease during mild stenosis, proving that transmural coronary autoregulatory function was well preserved in the preparation. During severe stenosis and complete occlusion, the coronary flow velocity significantly decreased. In the vehicle group microvessels <100 μm in inner diameter significantly dilated in response to the reduction in perfusion pressure (mild stenosis, 6.2±1.9%; severe stenosis, 21.1±4.4%; and complete occlusion, 16.8±5.9%; P<.05 versus baseline diameters). In the PTX group, microvessels did not dilate during each occlusion level (mild stenosis, -2.0±0.9%; severe stenosis, -3.9±1.9%; and complete occlusion, - 13.4±2.9%; P<.05 versus vehicle group). PTX did not affect the microvascular dilation caused by nitroprusside. The present data indicate that PTX- sensitive G protein is crucially involved in microvascular control during autoregulation and ischemia.
AB - GTP-binding regulatory proteins (G proteins) regulate various biological functions, but their participation in controlling coronary microvascular tone has not been established yet. The goal of the present study was to elucidate the role of pertussis toxin (PTX)-sensitive G protein in regulating coronary microvascular tone during autoregulation and ischemia. In 42 open-chest dogs, coronary arterial microvessels on the surface of the left ventricle were directly observed by epi-illuminated fluorescence microangiography using a floating objective system. PTX (300 ng/mL) was superfused onto the surface of the left ventricle for 2 hours to block G(i) and G(o) protein in epimyocardial coronary microvessels in vivo. PTX superfusion caused no change in the resting diameters of microvessels and significantly blocked the vasoconstriction induced by BHT 920 (a selective α2-agonist). After pretreatment with PTX or its vehicle, the left anterior descending coronary artery (LAD) was occluded by a hydraulic occluder to reduce coronary perfusion pressure (CPP) in a stepwise fashion. A mild stenosis (CPP, 60 mm Hg), a severe stenosis (CPP, .40 mm Hg), and complete occlusion were sequentially produced. Coronary flow velocity in the LAD distal to the stenotic site was continuously monitored. In both PTX and vehicle groups, flow velocity did not significantly decrease during mild stenosis, proving that transmural coronary autoregulatory function was well preserved in the preparation. During severe stenosis and complete occlusion, the coronary flow velocity significantly decreased. In the vehicle group microvessels <100 μm in inner diameter significantly dilated in response to the reduction in perfusion pressure (mild stenosis, 6.2±1.9%; severe stenosis, 21.1±4.4%; and complete occlusion, 16.8±5.9%; P<.05 versus baseline diameters). In the PTX group, microvessels did not dilate during each occlusion level (mild stenosis, -2.0±0.9%; severe stenosis, -3.9±1.9%; and complete occlusion, - 13.4±2.9%; P<.05 versus vehicle group). PTX did not affect the microvascular dilation caused by nitroprusside. The present data indicate that PTX- sensitive G protein is crucially involved in microvascular control during autoregulation and ischemia.
KW - arterioles
KW - coronary circulation
KW - guanine nucleotide regulatory protein
KW - microcirculation
KW - vasodilation
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U2 - 10.1161/01.RES.75.3.556
DO - 10.1161/01.RES.75.3.556
M3 - Article
C2 - 7914838
AN - SCOPUS:0028146230
VL - 75
SP - 556
EP - 566
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 3
ER -