Des-serine-proline brain natriuretic peptide 3-32 in cardiorenal regulation

Des-serine-proline brain natriuretic peptide 3-32 in cardiorenal regulation
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DOI:
10.1152/ajpregu.00569.2006
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发表时间:
2007-02-01
影响因子:
2.8
通讯作者:
Burnett, John C., Jr.
Burnett, John C., Jr.
中科院分区:
医学3区
文献类型:
--
作者:
Boerrigter, Guido;Costello-Boerrigter, Lisa C.;Burnett, John C., Jr.

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去丝氨酸脯氨酸脑钠肽3-32在心肾调节中的作用。Am J Physiol Regul Integr Comp Physiol 292:R897-R901,2007年。首次发表于2006年10月26日; doi:10.1152/ajpregu .00569.2006。脑钠肽(BNP 1-32)在维持心肾平衡中起重要的生理作用。最近,据报道,BNP 1-32被普遍存在的酶二肽基肽酶IV快速切割成BNP 3-32,其缺少BNP 1-32的两个NH 2-末端氨基酸。BNP 3-32在心肾调节中的生物活性尚不清楚。我们假设BNP 3-32在体内的血管舒张和利钠生物活性较BNP 1-32降低。将合成的人BNP 3-32和BNP 1-32给予8只麻醉的正常犬。基线测量后,给予BNP 1-32 30 ng(中心点)kg(-1中心点)min(-1),随后进行洗脱、输注后清除和等摩尔剂量BNP 3-32清除。在4项研究中,BNP 1-32和BNP 3-32输注顺序颠倒。通过分析从各自的输注前清除率到各自的输注清除率的变化来比较肽。肽之间的 *P < 0.05。与BNP 1-32不同,BNP 3-32不会降低平均动脉压(分别为0 +/- 1和-7 +/- 2* mmHg),也不会增加肾血流量(+12 +/- 10和+52 +/- 10* ml/min)。对心率和心输出量的影响相似。BNP 3-32组尿钠排泄增加128 +/- 18 mu eq/min,BNP 1-32组尿钠排泄增加338 +/- 40* mu eq/min。BNP 3-32组尿流量增加1.1 +/- 0.2 ml/min,BNP 1-32组尿流量增加2.8 +/- 0.4* ml/min。血浆BNP免疫反应性较低,BNP 3-32,表明加速降解。在这项研究中,与BNP 1-32相比,BNP 3-32显示出尿钠排泄和利尿减少以及缺乏血管舒张作用。
Des-serine-proline brain natriuretic peptide 3-32 in cardiorenal regulation. Am J Physiol Regul Integr Comp Physiol 292: R897-R901, 2007. First published October 26, 2006; doi: 10.1152/ajpregu .00569.2006.- Brain natriuretic peptide (BNP 1-32) plays an important physiologic role in cardiorenal homeostasis. Recently, it has been reported that BNP 1-32 is rapidly cleaved by the ubiquitous enzyme dipeptidyl peptidase IV to BNP 3-32, which lacks the two NH2-terminal amino acids of BNP 1-32. The bioactivity of BNP 3-32 in cardiorenal regulation is unknown. We hypothesized that BNP 3-32 has reduced vasodilating and natriuretic bioactivity compared with BNP 1-32 in vivo. Synthetic human BNP 3-32 and BNP 1-32 were administered to eight anesthetized normal canines. After baseline measurements, BNP 1-32 at 30 ng(center dot)kg(-1 center dot)min(-1) was administered, followed by a washout, a postinfusion clearance, and a clearance with an equimolar dose of BNP 3-32. In four studies, the sequence of BNP 1-32 and BNP 3-32 infusion was reversed. Peptides were compared by analyzing the changes from the respective preinfusion clearance to the respective infusion clearance. *P < 0.05 between peptides. BNP 3-32, unlike BNP 1-32, did not decrease mean arterial pressure (0 +/- 1 vs. -7 +/- 2* mmHg, respectively) and did not increase renal blood flow (+12 +/- 10 vs. +52 +/- 10* ml/min). Effects on heart rate and cardiac output were similar. Urinary sodium excretion increased 128 +/- 18 mu eq/min with BNP 3-32 and 338 +/- 40* mu eq/min with BNP 1-32. Urine flow increased 1.1 +/- 0.2 ml/min with BNP 3-32 and 2.8 +/- 0.4* ml/min with BNP 1-32. Plasma BNP immunoreactivity was lower with BNP 3-32, suggesting accelerated degradation. In this study, BNP 3-32 showed reduced natriuresis and diuresis and a lack of vasodilating actions compared with BNP 1-32.