Zhang Y, Legare D J, Geiger J D, Lautt W W
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
J Pharmacol Exp Ther. 1991 Sep;258(3):767-71.
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.
本研究调查了腺苷摄取抑制剂双嘧达莫对体内腺苷介导的血管舒张作用的影响。静脉内和门静脉内输注外源性腺苷（0.04 - 1.0 mg/kg/min），除了在较高测试剂量（0.4 - 1.0 mg/kg/min）时，不会再循环导致肠系膜上动脉传导（SMAC）增加或动脉血浆腺苷水平升高。然而，在给予双嘧达莫后，即使是低剂量（0.04 - 0.1 mg/kg/min）的外源性腺苷也能显著增加SMAC并提高动脉血浆腺苷浓度。增加的腺苷水平与SMAC变化百分比的增加高度相关，Rmax和EC50值分别为SMAC变化的193.4 +/- 27.3%和2.8 +/- 1.3 microM。推注剂量的8 - 苯基茶碱给药消除了双嘧达莫增强血管舒张的能力，但不影响异丙肾上腺素诱导的舒张。总之，这些结果表明，双嘧达莫对外源性腺苷血管舒张作用的增强是通过抑制体内腺苷摄取介导的，这增加了血浆腺苷作用于腺苷受体的可用性。
