Rongen G A, Brooks S C, Ando S i, Abramson B L, Floras J S
Division of Cardiology, Mount Sinai Hospital and the Centre for Cardiovascular Research, University of Toronto, Ontario, Canada M5G 1X5.
J Clin Invest. 1998 Feb 15;101(4):769-76. doi: 10.1172/JCI480.
We tested the hypothesis that endogenous angiotensin II participates in the direct and reflex effects of adenosine on the sympathetic nervous system. Nine healthy men were studied after 1 wk of the angiotensin II type I receptor antagonist losartan (100 mg daily) or placebo, according to a double-blind randomized crossover design. Bilateral forearm blood flows, NE appearance rates, and total body NE spillover were determined before and during graded brachial arterial infusion of adenosine (0.5, 1.5, 5, and 15 microg/100 ml forearm tissue) and nitroprusside. Adenosine increased total body NE spillover (P < 0.05) whereas nitroprusside did not. Losartan lowered BP (P < 0.05), had no effect on total body NE spillover at rest, or forearm vasodilation during either infusion, but reduced the systemic noradrenergic response to adenosine from 1.0+/-0.4 nmol/min on the placebo day to 0.2+/-0.3 nmol/min (P < 0.01), and forearm NE appearance rate in response to adenosine was lower in the infused, as compared with the contralateral arm (P = 0.04). The sympatho-excitatory reflex elicited by adenosine is mediated through pathways involving the angiotensin II type I receptor. Interactions between adenosine and angiotensin II may assume importance during ischemia or congestive heart failure and could contribute to the benefit of converting enzyme inhibition in these conditions.
我们检验了内源性血管紧张素II参与腺苷对交感神经系统的直接和反射作用这一假设。按照双盲随机交叉设计，对9名健康男性进行了研究，他们在服用血管紧张素II 1型受体拮抗剂氯沙坦（每日100毫克）或安慰剂1周后接受观察。在肱动脉分级输注腺苷（0.5、1.5、5和15微克/100毫升前臂组织）和硝普钠之前及期间，测定双侧前臂血流量、去甲肾上腺素（NE）出现率和全身NE溢出量。腺苷增加了全身NE溢出量（P<0.05），而硝普钠则没有。氯沙坦降低了血压（P<0.05），对静息时的全身NE溢出量或输注期间的前臂血管舒张均无影响，但将对腺苷的全身去甲肾上腺素能反应从安慰剂日的1.0±0.4纳摩尔/分钟降至0.2±0.3纳摩尔/分钟（P<0.01），并且与对侧手臂相比，输注侧对腺苷反应的前臂NE出现率更低（P = 0.04）。腺苷引发的交感兴奋反射是通过涉及血管紧张素II 1型受体的途径介导的。腺苷与血管紧张素II之间的相互作用在缺血或充血性心力衰竭期间可能具有重要意义，并且可能有助于在这些情况下使用转换酶抑制剂带来的益处。
