Role of pertussis toxin-sensitive G protein in metabolic vasodilation of coronary microcirculation

We have previously demonstrated that pertussis toxin (PTX) sensitive G prot ein (G(PTX)) plays a major role in coronary microvascular vasomotion during hypoperfusion. We aimed to elucidate the role of G(PTX) during increasing metabolic demand. In 18 mongrel dogs, coronary arteriolar diameters were me asured by fluorescence microangiography using a floating objective. Myocard ial oxygen consumption (M(V)over dot O-2) was increased by rapid left atria l pacing. In six dogs, PTX (300 ng/ml) was superfused onto the heart surfac e for 2 h to locally block G(PTX). In eight dogs, the vehicle (Krebs soluti on) was superfused in the same way. Before and after each treatment, the di ameters were measured during control (130 beats/min) and rapid pacing (260 beats/min) in each group. Metabolic stimulation before and after the vehicl e treatment caused 8.6 +/- 1.8 and 16.1 +/- 3.6% dilation of coronary arter ioles <100 mu m in diameter (57 +/- 8 mm at control, n = 10), respectively. PTX treatment clearly abolished the dilation of arterioles (12.8 +/- 2.5% before and 0.9 +/- 1.6% after the treatment, P < 0.001 vs. vehicle; 66 +/- 8 mu m at control, n = 11) in response to metabolic stimulation. The increa ses in M(V) over dot O-2 and coronary flow velocity were comparable between the vehicle and PTX groups. In four dogs, 8-phenyltheophylline (10 mu M, s uperfusion for 30 min) did not affect the metabolic dilation of arterioles (15.3 +/- 2.0% before and 16.4 +/- 3.8% after treatment; 84.3 +/- 11.0 mu m at control, n = 8). Thus we conclude that G(PTX) plays a major role in reg ulating the coronary microvascular tone during active hyperemia, and adenos ine does not contribute to metabolic vasodilation via G(PTX) activation.