摘要
BackgroundBrain natriuretic 肽(BNP ) 在在发行量的底层是通常在场的,但是它在心失败题目(CHF ) 与拥挤的度同时被提高。BNP 有 natriuretic 效果并且是有势力血管扩张药。BNP 能是在 CHF 的一种治疗学的选择,这被建议。然而,我们要求了在 CHF 的传播 BNP 的高水平可以 downregulate microvascular natriuretic 受体的反应。这被比较 15 个 CHF 病人测试(BNP >;3000 ng/L ) 与 10 匹配的、健康 controls.MethodsCutaneous microvascular 血,在前臂的流动被激光 Doppler Flowmetry 测量。本地加热(+44 °; C, 10 min ) 被用来唤起一个最大的本地扩张器 BNP 或醋胆素(ACh ) 的 response.ResultsNon 侵略的 iontophoretic 管理,一个已知的内皮细胞层依赖者扩张器,在本地流动得到了增加。氮的氧化物 synthase 禁止者, l-N-Arginine- 甲基酉旨(L 名字) ,堵住了 BNP 反应(在控制) 。有趣地,对在 CHF 病人的 BNP 的回答被归结为在健康控制看见的大约三分之一那些(的增加流动:251% 在 CHF 对 908% 在控制;P <;0.001 ) 。相反,对 ACh 并且到本地加热的血管扩张药回答仅仅有点在 CHF 病人被稀释。因此,发信号的扩张器能力和氮的氧化物没被影响到象调停 BNP 的膨胀的一样的程度,第一次显示后者 response.ConclusionsThe 调查结果表演的特定的 downregulation 对 BNP 的 microvascular 回答显著地在 CHF 病人被减少。这与 BNP 受体功能的假设一致是在 CHF 的 downregulated。
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.
关键词
血管扩张剂
利钠肽
反应
患者
人体老化
心脏
衰竭
显示
Heart failure
Cutaneous microcirculation
Endothelial responses
Acetylcholine, Brain natriuretic peptide
Nitric oxide