Rooney M W, Crystal G J, Salem M R, Paulissian R
Department of Anesthesiology, Illinois Masonic Medical Center, Chicago 60657.
Anesth Analg. 1989 Mar;68(3):261-9.
Previous pharmacologic studies indicating competitive interactions between adenosine and nifedipine at the adenosine vascular receptor suggest that adenosine may be a less effective hypotensive drug after pretreatment with nifedipine. This hypothesis was tested in 18 pentobarbital-anesthetized, open-chest dogs by evaluating the hypotensive effects and regional hemodynamic responses to 60-minute intravenous adenosine infusions before and after bolus injection of nifedipine (20 micrograms/kg, IV). Regional blood flow was measured with 15-microns radioactive microspheres. Before nifedipine, infusion of adenosine at a rate of 126 +/- 30 mumol/min caused a 50% reduction in mean aortic pressure that in the presence of no change in aortic blood flow was attributable to a proportional decrease in systemic vascular resistance. These systemic effects were associated with heterogeneous changes in regional blood flow; blood flow decreased in the renal cortex (-68%), pancreas (-50%), spleen (-77%), and skin (-61%); increased in the left (+112%) and right (+265%) ventricular myocardium; and did not change significantly in the duodenum, liver, skeletal muscle, or brain. Nifedipine did not alter the dose requirement or time course of the adenosine-induced hypotensive response or affect the associated systemic hemodynamic changes. Furthermore, nifedipine caused only minor alterations in the regional blood flow changes during adenosine-induced hypotension. Apparently the high plasma levels of adenosine required for controlled hypotension in the present study were sufficient to overcome the blocking influence of nifedipine at the adenosine vascular receptor. The study demonstrates that the hypotensive action of adenosine remains unimpaired after pretreatment with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)
以往的药理学研究表明,腺苷与硝苯地平在腺苷血管受体处存在竞争性相互作用,这提示在硝苯地平预处理后,腺苷可能是一种效果较差的降压药。在18只戊巴比妥麻醉、开胸的犬中对这一假说进行了验证,通过评估在静脉推注硝苯地平(20微克/千克,静脉注射)前后60分钟静脉输注腺苷的降压效果和局部血流动力学反应。用15微米的放射性微球测量局部血流量。在给予硝苯地平之前,以126±30微摩尔/分钟的速率输注腺苷导致平均主动脉压降低50%,在主动脉血流量无变化的情况下,这归因于全身血管阻力成比例下降。这些全身效应与局部血流的异质性变化相关;肾皮质(-68%)、胰腺(-50%)、脾脏(-77%)和皮肤(-61%)的血流量减少;左(+112%)和右(+265%)心室心肌的血流量增加;十二指肠、肝脏、骨骼肌或大脑的血流量无显著变化。硝苯地平未改变腺苷诱导的降压反应的剂量需求或时间进程,也未影响相关的全身血流动力学变化。此外,硝苯地平在腺苷诱导的低血压期间仅引起局部血流变化的轻微改变。显然,本研究中控制性低血压所需的高血浆腺苷水平足以克服硝苯地平在腺苷血管受体处的阻断作用。该研究表明,硝苯地平预处理后腺苷的降压作用仍然未受损害。(摘要截短于250字)