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 micrograms.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 micrograms.kg-1.min-1) produced 95 +/- 3% (P less than 0.001, n = 6) attenuation of exogenous adenosine-induced vasodilation at constant pressure, a 28 +/- 5% (P less than 0.01, n = 6) attenuation of reactive hyperemia, and a 24 +/- 6% (P less than 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.
Lee
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SC
Department of Physiology, Texas College of Osteopathic Medicine, Fort Worth 76107-2690.
Mallet
R T
RT
Shizukuda
Y
Y
Williams
A G
AG
Downey
H F
HF
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D011312:Pressure; D012996:Solutions; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D012996:Solutions; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine