Komaru T, Wang Y, Akai K, Sato K, Sekiguchi N, Sugimura A, Kumagai T, Kanatsuka H, Shirato K
First Department of Internal Medicine, Tohoku University, School of Medicine, Sendai, Japan.
Circ Res. 1994 Sep;75(3):556-66. doi: 10.1161/01.res.75.3.556.
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 Gi 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 alpha 2-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 microns 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.
GTP结合调节蛋白（G蛋白）调节多种生物学功能，但其在控制冠状动脉微血管张力中的作用尚未明确。本研究的目的是阐明百日咳毒素（PTX）敏感的G蛋白在自动调节和缺血过程中调节冠状动脉微血管张力的作用。在42只开胸犬中，使用浮动物镜系统通过落射荧光微血管造影术直接观察左心室表面的冠状动脉微血管。将PTX（300 ng/mL）灌注到左心室表面2小时，以在体内阻断心外膜冠状动脉微血管中的Gi和G(o)蛋白。PTX灌注未引起微血管静息直径的变化，并显著阻断了BHT 920（一种选择性α2激动剂）诱导的血管收缩。在用PTX或其溶媒预处理后，用液压闭塞器闭塞左前降支冠状动脉（LAD），以逐步降低冠状动脉灌注压（CPP）。依次产生轻度狭窄（CPP，60 mmHg）、重度狭窄（CPP，40 mmHg）和完全闭塞。连续监测狭窄部位远端LAD的冠状动脉血流速度。在PTX组和溶媒组中，轻度狭窄期间血流速度均未显著降低，证明在该制备中跨壁冠状动脉自动调节功能良好。在重度狭窄和完全闭塞期间，冠状动脉血流速度显著降低。在溶媒组中，内径<100微米的微血管因灌注压降低而显著扩张（轻度狭窄，6.2±1.9%；重度狭窄，21.1±4.4%；完全闭塞，16.8±5.9%；与基线直径相比，P<.05）。在PTX组中，在每个闭塞水平微血管均未扩张（轻度狭窄，-2.0±0.9%；重度狭窄，-3.9±1.9%；完全闭塞，-13.4±2.9%；与溶媒组相比，P<.05）。PTX不影响硝普钠引起的微血管扩张。目前的数据表明，PTX敏感的G蛋白在自动调节和缺血过程中对微血管控制至关重要。
