Dilazep potentiation of adenosine-mediated superior mesenteric arterial vasodilation.
The present study investigated the effects of dilazep, an inhibitor of adenosine uptake, on adenosine-mediated vasodilation in vivo. Intravenous and intraportal venous infusions of exogenous adenosine (0.04-1.0 mg/kg/min) did not recirculate to cause increases in superior mesenteric arterial conductance (SMAC) or arterial plasma adenosine levels except at the higher doses tested (0.4-1.0 mg/kg/min). After administration of dilazep, however, even low doses (0.04-0.1 mg/kg/min) of exogenous adenosine significantly increased SMAC and elevated arterial plasma adenosine concentration. The increased adenosine levels were highly correlated with the increased percentage of change of SMAC and values for Rmax and EC50 were 193.4 +/- 27.3% change of SMAC and 2.8 +/- 1.3 microM, respectively. Administration of bolus doses of 8-phenyltheophylline abolished the ability of dilazep to potentiate vasodilation, but did not affect isoproterenol-induced relaxation. Together, these results suggest that potentiation of the vasodilating effect of exogenous adenosine by dilazep is mediated through inhibition of adenosine uptake in vivo which increases the availability of plasma adenosine to act on adenosine receptors.
Zhang
Y
Y
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Legare
D J
DJ
Geiger
J D
JD
Lautt
W W
WW
D000241:Adenosine / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D004109:Dilazep / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D011983:Receptors, Purinergic; D014665:Vasodilator Agents; D013806:Theophylline; C028322:8-phenyltheophylline; D004109:Dilazep; D000241:Adenosine