Casserly Brian, Klinger James R
Division of Pulmonary and Critical Care Medicine, The Memorial Hospital of Rhode Island, Pawtucket, RI, USA.
Drug Des Devel Ther. 2009 Dec 29;3:269-87. doi: 10.2147/dddt.s4805.
B-type natriuretic peptide (BNP) is a member of the natriuretic peptide family, a group of widely distributed, but evolutionarily conserved, polypeptide mediators that exert myriad cardiovascular effects. BNP is a potent vasodilator with mitogenic, hypertrophic and pro-inflammatory properties that is upregulated in pulmonary hypertensive diseases. Circulating levels of BNP correlate with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension (PAH). Elevated plasma BNP levels are associated with increased mortality in patients with PAH and a fall in BNP levels after therapy is associated with improved survival. These findings have important clinical implications in that a noninvasive blood test may be used to identify PAH patients at high-risk of decompensation and to guide pulmonary vasodilator therapy. BNP also has several biologic effects that could be beneficial to patients with PAH. However, lack of a convenient method for achieving sustained increases in circulating BNP levels has impeded the development of BNP as a therapy for treating pulmonary hypertension. New technologies that allow transdermal or oral administration of the natriuretic peptides have the potential to greatly accelerate research into therapeutic use of BNP for cor pulmonale and pulmonary vascular diseases. This review will examine the basic science and clinical research that has led to our understanding of the role of BNP in cardiovascular physiology, its use as a biomarker of right ventricular function and its therapeutic potential for managing patients with pulmonary vascular disease.
B型利钠肽(BNP)是利钠肽家族的成员,利钠肽家族是一组分布广泛但在进化上保守的多肽介质,具有多种心血管效应。BNP是一种强效血管舒张剂,具有促有丝分裂、肥大和促炎特性,在肺动脉高压疾病中上调。肺动脉高压(PAH)患者的循环BNP水平与平均肺动脉压(mPAP)和肺血管阻力(PVR)相关。PAH患者血浆BNP水平升高与死亡率增加相关,治疗后BNP水平下降与生存率提高相关。这些发现具有重要的临床意义,因为无创血液检测可用于识别失代偿高风险的PAH患者并指导肺血管舒张剂治疗。BNP还具有几种可能对PAH患者有益的生物学效应。然而,缺乏一种方便的方法来持续提高循环BNP水平阻碍了BNP作为治疗肺动脉高压的疗法的发展。允许经皮或口服给予利钠肽的新技术有可能极大地加速对BNP用于治疗肺心病和肺血管疾病的治疗用途的研究。本综述将探讨基础科学和临床研究,这些研究使我们了解了BNP在心血管生理学中的作用、其作为右心室功能生物标志物的用途以及其治疗肺血管疾病患者的潜力。