Angiotensin II AT1 receptor antagonism prevents detrimental renal actions of acute diuretic therapy in human heart failure
Angiotensin II AT1 receptor antagonism prevents detrimental renal actions of acute diuretic therapy in human heart failure
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DOI：
10.1152/ajprenal.00337.2002
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发表时间：
2003-05-01
影响因子：
4.2
通讯作者：
Burnett, JC
中科院分区：
文献类型：
--
作者：
Chen, HH;Redfield, MM;Burnett, JC
尽管利尿剂诱导的尿钠排泄可有效缓解充血性心力衰竭（CHF）的水肿症状，但可能与肾小球滤过率（GFR）和有效肾血浆流量（ERPF）降低相关，随后可能缩短尿钠排泄的持续时间。此外，最近的研究报告称，GFR的保留是人CHF生存的重要预测因素。我们假设，在有症状的人CHF中，对呋塞米的急性有害的肾脏血流动力学和肾小管反应将被氯沙坦的AT（1）受体阻断剂减弱。在一项双盲、安慰剂对照的交叉研究中，我们确定了10名CHF受试者在急性AT（1）受体拮抗剂（氯沙坦，MSD，50 mg口服）存在下对呋塞米（40 mg，口服）与安慰剂的肾血流动力学和肾小管作用以及醛固酮反应（纽约心脏协会II- III）。呋塞米联合安慰剂可增加钠排泄，降低ERPF和GFR（与基线相比P < 0.05）。4 h后尿钠排泄量较基线减少（P < 0.05）。相比之下，呋塞米联合氯沙坦导致钠排泄增加，但ERPF和GFR没有降低（与安慰剂相比，P < 0.05）。4小时后，与安慰剂组相比，钠排泄量更大。重要的是，安慰剂组的血浆醛固酮有升高的趋势，而仅氯沙坦组的血浆醛固酮降低（与基线相比P < 0.05）。这些研究强调了AT（1）受体在介导利尿剂对人类CHF的肾脏和肾上腺有害特性方面的病理生理作用。AT（1）受体拮抗剂除了抑制醛固酮分泌外，还能在急性利尿治疗期间保护GFR和肾血流量，并增强钠排泄。这些发现支持AT（1）受体阻滞剂用于需要急性利尿剂的人CHF，以改善肾血流动力学和肾小管功能并抑制醛固酮。
Although effective in relieving symptoms of edema in congestive heart failure ( CHF), diuretic- induced natriuresis may be associated with reductions in glomerular filtration rate ( GFR) and effective renal plasma flow ( ERPF), which subsequently may reduce the duration of natriuresis. Moreover, recent studies have reported that the preservation of GFR is an important predictor of survival in human CHF. We hypothesized that the acute detrimental renal hemodynamic and tubular responses to furosemide in symptomatic human CHF will be attenuated by AT(1) receptor blockade with losartan. We defined the renal hemodynamic and tubular actions and aldosterone responses to furosemide ( 40 mg, orally) in the presence of acute AT(1) receptor antagonism ( losartan, MSD, 50 mg orally) vs. placebo in 10 subjects with CHF ( New York Heart Association II- III) in a double- blind, placebo- controlled crossover study. Furosemide with placebo increased sodium excretion and reduced ERPF and GFR ( P < 0.05 vs. baseline). After 4 h, sodium excretion compared with baseline was decreased ( P < 0.05). In contrast, furosemide with losartan resulted in a greater increase in sodium excretion but without reductions in ERPF and GFR ( P < 0.05 vs. placebo). After 4 h, sodium excretion was greater compared with the placebo group. Importantly, plasma aldosterone tended to increase in the placebo group, whereas it was decreased ( P < 0.05 vs. baseline) only in the losartan group. These studies underscore the pathophysiological role of the AT(1) receptor in mediating detrimental renal and adrenal properties of diuretics in human CHF. AT(1) receptor antagonism preserves GFR and renal blood flow and enhances sodium excretion during acute diuretic therapy in addition to inhibiting aldosterone secretion. These findings support the use of AT(1) receptor blockade for human CHF requiring acute diuretics to improve renal hemodynamic and tubular function and to suppress aldosterone.