CAFFEINE ATTENUATES THE RENAL VASCULAR-RESPONSE TO ANGIOTENSIN-II INFUSION
CAFFEINE ATTENUATES THE RENAL VASCULAR-RESPONSE TO ANGIOTENSIN-II INFUSION
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DOI：
10.1161/01.hyp.22.6.847
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发表时间：
1993-12-01
期刊：
影响因子：
8.3
通讯作者：
NADEAU, J
中科院分区：
文献类型：
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作者：
BROWN, NJ;RYDER, D;NADEAU, J
非调节已被提出作为人类原发性高血压的一种中间表型。该特征表现为对短期血管紧张素II（Ang II）输注的醛固酮和肾血浆流量反应减弱。组织中Ang II水平升高或组织中腺苷水平降低可能是对Ang II敏感性降低的原因。支持后一种可能性的是，内源性腺苷已被证明在动物中有助于对Ang II的肾血管收缩反应。因此，我们检验了内源性腺苷有助于调节钠充足的人体肾血浆流量这一假设。在一项单盲、安慰剂对照研究中，我们检测了长期给予腺苷受体拮抗剂咖啡因对6名钠充足的正常血压受试者的基线肾血浆流量以及对短期Ang II输注的肾血浆流量反应的影响。对氨基马尿酸清除率用于评估肾血浆流量。在有和没有咖啡因（250mg，每日三次，共7天）的情况下，以分级剂量（0.3 - 3ng/kg每分钟）输注Ang II。在每次输注Ang II前后测量血压、血浆肾素活性、Ang II、电解质和对氨基马尿酸清除率。咖啡因既没有改变基线血压，也没有改变对Ang II的血压反应，但确实将基线血浆肾素活性从0.72±0.09提高到1.42±0.26ng血管紧张素I/mL每小时（P = 0.01）。咖啡因将基线肾血浆流量从553±38降低到476±31mL/min每1.73m²（P = 0.004），并减弱了对3ng/kg每分钟Ang II输注的肾血浆流量反应（-106.5±25.2与-170.5±18mL/min每1.73m²，P = 0.006）。这些数据表明，咖啡因调节基线肾血浆流量以及对外源性Ang II的肾血浆流量反应，因此支持腺苷有助于调节钠充足的人体肾血浆流量这一假设。因此，非调节可能是部分后天获得的，在定义调节表型的研究中必须控制咖啡因的摄入。
Non-modulation has been proposed as an intermediate phenotype in human essential hypertension. The trait is characterized by blunted aldosterone and renal plasma flow responses to short-term angiotensin II (Ang II) infusion. Elevated tissue Ang II levels or decreased tissue adenosine levels could account for this decreased sensitivity to Ang II. In support of the latter possibility, endogenous adenosine has been shown to contribute to the renal vasoconstrictive response to Ang II in animals. We therefore tested the hypothesis that endogenous adenosine contributes to modulation of renal plasma flow in sodium-replete humans. We examined the effect of long-term administration of the adenosine receptor antagonist caffeine on baseline renal plasma flow and on the renal plasma how response to short-term Ang II infusion in six salt-replete normotensive subjects in a single-blind, placebo-controlled study. para-Aminohippurate clearance was used to assess renal plasma flow. Ang II was infused in graded doses (0.3 to 3 ng/kg per minute) in the presence and absence of caffeine (250 mg P circle dot TID for 7 days). Blood pressure, plasma renin activity, Ang II, electrolytes, and para-aminohippurate clearance were measured before and after each dose of Ang II. Caffeine did not alter either baseline blood pressure or the blood pressure response to Ang II but did increase baseline plasma renin activity from 0.72+/-0.09 to 1.42+/-0.26 ng angiotensin I/mL per hour (P=.01). Caffeine decreased the baseline renal plasma flow from 553+/-38 to 476+/-31 mL/min per 1.73 m(2) (P=.004) and attenuated the renal plasma flow response to a 3 ng/kg per minute infusion of Ang II (-106.5+/-25.2 versus -170.5+/-18 mL/min per 1.73 m(2), P=.006). These data demonstrate that caffeine modulates baseline renal plasma flow and the renal plasma flow response to exogenous Ang II and therefore support the hypothesis that adenosine contributes to modulation of renal plasma flow in salt-replete humans. Thus, non-modulation may be partially acquired, and caffeine consumption must be controlled in studies that define modulation phenotype.