Noncompetitive antagonism of adenosine by caffeine on the hepatic and superior mesenteric arteries of anesthetized cats.
Caffeine (3-93 mg/kg iv.) did not alter systemic blood pressure, central venous or portal venous pressure or blood flow or vascular conductance in the hepatic artery (HA) or superior mesenteric artery (SMA) of cats anesthetized with pentobarbital or chloralose. Caffeine did not antagonize the physiological response (adenosine-mediated dilation) of the HA induced by reduced portal flow but did produce a noncompetitive antagonism of the vasodilation induced by exogenous adenosine. Pharmacodynamic data for the HA and SMA indicated that the maximum response calculated (Rmax) of adenosine was suppressed but the dose producing half Rmax was unaltered by caffeine. Although the Rmax for adenosine-induced dilation of the HA was suppressed in a dose-dependent manner, the Rmax for caffeine's effect was only 60%, thus indicating that about 40% of the dilator effect of adenosine could not be suppressed at any dose of caffeine. The dilator response to isoproterenol was unaffected by caffeine. The observation that 40% of the dilator effect of adenosine was also not suppressible by caffeine suggests that adenosine causes dilation by two different mechanisms, one of which (perhaps cyclic AMP-dependent) is not affected by caffeine. To produce a 50% inhibition of the HA Rmax for adenosine, a dose of 33 mg/kg of caffeine was required (53 mg/kg in the SMA); doses of 93 mg/kg consistently produced cardiac arrhythmias. It is thus unlikely that even very heavy caffeine consumption would lead to altered hepatic blood flow or altered regulation of adenosine-mediated vascular responses.
Lautt
W W
WW
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
D000241:Adenosine / Q000037:antagonists & inhibitors*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology*; D002415:Cats; D002698:Chloralose / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006499:Hepatic Artery / Q000187:drug effects*; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D010424:Pentobarbital / Q000494:pharmacology
D002698:Chloralose; D002110:Caffeine; D010424:Pentobarbital; D000241:Adenosine; D007545:Isoproterenol