Intact acute cardiorenal and humoral responsiveness following chronic subcutaneous administration of the cardiac peptide BNP in experimental heart failure
Intact acute cardiorenal and humoral responsiveness following chronic subcutaneous administration of the cardiac peptide BNP in experimental heart failure
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DOI：
10.1016/j.ejheart.2005.12.005
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发表时间：
2006-11-01
影响因子：
18.2
通讯作者：
Burnett, John C., Jr.
中科院分区：
文献类型：
--
作者：
Chen, Horng H.;Schirger, John A.;Burnett, John C., Jr.
背景：脑钠肽（BNP）是一种由第二信使环鸟苷酸（cGMP）介导的心脏肽，具有扩血管、利钠和利尿作用。我们以前已经表明，慢性皮下（SQ）管理BNP在实验性CHF导致改善血流动力学和卸载的心脏。然而，这是否会导致对外源性BNP的耐受性的发展尚不清楚。本研究扩展了我们先前的研究，并比较了急性给予SQ BNP的心肾效应（5 μ g/kg）在一组快速心室起搏诱导CHF的犬（n = 5）中（180 bpm，持续10天）给另一组CHF犬（n = 6），这些犬接受慢性SQ BNP（5 μ g/kg），每日3次，共10天。SQ BNP急性给药导致血浆cGMP水平和血浆cGMP水平相似升高。在慢性SQ BNP治疗组和未治疗CHF组中，尿cGMP排泄（UcGMPV）（35 +/- 5 vs. 29 +/- 2 pmol/ml）和尿cGMP排泄（6000 +/- 1000 vs. 4000 +/- 600 pmol/min）（P > 0.05）。这些都与降低心脏充盈压和增加尿流量，这也是相似的两个group.Conclusion：在实验性CHF，慢性SQ BNP管理并没有导致发展的耐受性，表现为增加血浆cGMP和UcGMPV后，急性管理SQ BNP。这可能具有重要的临床意义，表明慢性BNP给药不会导致对急性BNP给药的耐受性发展。(c)2006年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Background: BNP is a cardiac peptide with vasodilating, lusitropic and natriuretic properties mediated by the second messenger cGMP. We have previously shown that chronic subcutaneous (SQ) administration of BNP in experimental CHF resulted in improved haemodynamics and unloading of the heart. However, it is unknown if this will lead to the development of tolerance to exogenous BNP.Methods: The current study extends our previous study and compares the cardiorenal effects of acute administration of SQ BNP (5 mu g/kg) in a group of dogs (n = 5) with rapid ventricular pacing induced CHF (180 bpm for 10 days) to a separate group of CHF dogs (n = 6), who received chronic SQ BNP (5 mu g/kg) three times a day for 10 days.Results: Acute administration of SQ BNP resulted in similar increases in both plasma cGMP (35 +/- 5 vs. 29 +/- 2 pmol/ml) and urinary cGMP excretion (UcGMPV) (6000 +/- 1000 vs. 4000 +/- 600 pmol/min) in both the Chronic SQ BNP treated and the Untreated CHF groups (P > 0.05). These were associated with decreased cardiac filling pressures and increased urine flow, which were also similar in both groups.Conclusion: In experimental CHF, chronic SQ BNP administration did not result in the development of tolerance as demonstrated by increases in both plasma cGMP and UcGMPV following acute administration of SQ BNP. This may have important clinical implications, suggesting that chronic BNP administration does not lead to the development of tolerance to acute BNP administration. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.