Brain natriuretic peptide is a potent vasodilator in aged human microcircula- tion and shows a blunted response in heart failure patients

作     者：Marie-Louise Edvinsson Erik Uddman Lars Edvinsson Sven E. Andersson 

作者机构：Department of Emergency and Internal Medicine Institute of Clinical Sciences Lund University Lund University Hospital SE- 221 85 Lund Sweden 

出 版 物：《Journal of Geriatric Cardiology》 (老年心脏病学杂志（英文版）)

年 卷 期：2014年第11卷第1期

页      面：50-56页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 10[医学] 

基　　金：supported by the Lisa & Johan Gronbergs Stiftelse  SEB Enskilda Banken  Stockholm  Sweden 

主　　题：Heart failure Cutaneous microcirculation Endothelial responses Acetylcholine, Brain natriuretic peptide Nitric oxide 

摘      要：Background Brain natriuretic peptide （BNP） is normally present in low levels in the circulation, but it is elevated in parallel with the degree of congestion in heart failure subjects （CHF）. BNP has natriuretic effects and is a potent vasodilator. It is suggested that BNP could be a therapeutic alternative in CHF. However, we postulated that the high levels of circulating BNP in CHF may downregulate the response of microvascular natriuretic receptors. This was tested by comparing 15 CHF patients （BNP 〉 3000 ng/L） with 10 matched, healthy controls. Methods Cutaneous microvascular blood flow in the forearm was measured by laser Doppler Flowmetry. Local heating （＋44°C, 10 min） was used to evoke a maximum local dilator response. Results Non-invasive iontophoretic administration of either BNP or acetylcholine （ACh）, a known endothelium-dependent dilator, elicited an increase in local flow. The nitric oxide synthase inhibitor, l-N-Arginine- methyl-ester （L-NAME）, blocked the BNP response （in controls）. Interestingly, responses to BNP in CHF patients were reduced to about one third of those seen in healthy controls （increase in flow： 251% in CHF vs. 908% in controls; P 〈 0.001）. In contrast, the vasodilator responses to ACh and to local heating were only somewhat attenuated in CHF patients. Thus, dilator capacity and nitric oxide signalling were not af- fected to the same extent as BNP-mediated dilation, indicating a specific downregulation of the latter response. Conclusions The findings show for the first time that microvascular responses to BNP are markedly reduced in CHF patients. This is consistent with the hypothesis of BNP receptor function is downregulated in CHF.