PERTUSSIS-TOXIN-SENSITIVE G-PROTEIN MEDIATES CORONARY MICROVASCULAR CONTROL DURING AUTOREGULATION AND ISCHEMIA IN CANINE HEART

GTP-binding regulatory proteins (G proteins) regulate various biologic al functions, but their participation in controlling coronary microvas cular tone has not been established yet. The goal of the present study was to elucidate the role of pertussis toxin (PTX)-sensitive G protei n 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-illuminat ed fluorescence microangiography using a floating objective system. PT X (300 ng/mL) was superfused onto the surface of the left ventricle fo r 2 hours to block G(i) and G(o) protein in epimyocardial coronary mic rovessels in vivo. PTX superfusion caused no change in the resting dia meters 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 perfusio n pressure (CPP) in a stepwise fashion. A mild stenosis (CPP, 60 mm Hg ), a severe stenosis (CPP, 40 mm Hg), and complete occlusion were sequ entially produced. Coronary flow velocity in the LAD distal to the ste notic site was continuously monitored. In both PTX and vehicle groups, flow velocity did not significantly decrease during mild stenosis, pr oving that transmural coronary autoregulatory function was well preser ved in the preparation. During severe stenosis and complete occlusion, the coronary flow velocity significantly decreased. In the vehicle gr oup, microvessels <100 mu m 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 d id net 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 dilat ion caused by nitroprusside. The present data indicate that PTX-sensit ive G protein is crucially involved in microvascular control during au toregulation and ischemia.