Canine coronary vasodepressor responses to hypoxia are attenuated but not abolished by 8-phenyltheophylline

The purpose of this study was twofold: 1) to verify a report that a suspension of 8-phenyltheophylline (8-PT) completely abolished hypoxia- induced coronary vasodilation [H. M. Wei, Y. H. Kang, and G. F. Merrill. Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H1043-H1048, 1989] and 2) to determine the effect of dissolved 8-PT on hypoxic hyperemia. The left anterior descending coronary artery of anesthetized dogs was cannulated and perfused at either constant flow or constant pressure. An 8-PT suspension (40 μg·kg^-1·min^-1) produced a twofold elevation of coronary perfusion pressure at constant flow, a 97% decrease in coronary flow at constant pressure, and regional akinesia in both conditions. The coronary vasculature was unresponsive to 60-s coronary occlusion, exogenous adenosine, and hypoxia after infusion of the 8-PT suspension. These findings are consistent with obstruction of the coronary microvasculature by the 8-PT suspension. An 8-PT solution (40 μg·kg^-1·min^-1) produced 95 ± 3% (P < 0.001, n = 6) attenuation of exogenous adenosine-induced vasodilation at constant pressure, a 28 ± 5% (P < 0.01, n = 6) attenuation of reactive hyperemia, and a 24 ± 6% (P < 0.05, n = 6) decrease in hypoxia-induced vasodilation. An 8-PT solution had no effect on systolic segment length shortening and myocardial oxygen consumption. We conclude that 8-PT, when in solution, attenuates but does not abolish the coronary vasodilatory response to hypoxia. Hence, adenosine appears to contribute to hypoxia-induced vasodilation but is not uniquely responsible for the hyperemic response.