Lee Candace Y W, Burnett John C
Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55906, USA.
Heart Fail Rev. 2007 Jun;12(2):131-42. doi: 10.1007/s10741-007-9016-3.
Since the discovery of atrial natriuretic factor by de Bold et al., there has been tremendous progress in our understanding of the physiologic, diagnostic and therapeutic roles of the natriuretic peptides (NPs) in health and disease. Natriuretic peptides are endogenous hormones that are released by the heart in response to myocardial stretch and overload. Three mammalian NPs have been identified and characterized, including atrial natriuretic peptide (ANP or atrial natriuretic factor), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). In addition, Dendroaspis natriuretic peptide (DNP) has been isolated from the venom of Dendroaspis angusticeps (the green mamba snake), and urodilatin from human urine. These peptides are structurally similar and they consist of a 17-amino-acid core ring and a cysteine bridge. Both ANP and BNP bind to natriuretic peptide receptor A (NPR-A) that are expressed in the heart and other organs. Activation of NPR-A generates an increase in cyclic guanosine monophosphate, which mediates natriuresis, inhibition of renin and aldosterone, as well as vasorelaxant, anti-fibrotic, anti-hypertrophic, and lusitropic effects. The NP system thus serves as an important compensatory mechanism against neurohumoral activation in heart failure. This provides a strong rationale for the use of exogenous NPs in the management of acutely decompensated heart failure. In this article, the therapeutic applications of NPs in the acute heart failure syndromes are reviewed. Emerging therapeutic agents and areas for future research are discussed.
自从德博尔德等人发现心房利钠因子以来，我们对利钠肽（NPs）在健康和疾病中的生理、诊断及治疗作用的理解取得了巨大进展。利钠肽是心脏在应对心肌牵张和负荷过重时释放的内源性激素。已鉴定并表征了三种哺乳动物利钠肽，包括心房利钠肽（ANP或心房利钠因子）、B型利钠肽（BNP）和C型利钠肽（CNP）。此外，已从绿曼巴蛇（Dendroaspis angusticeps）的毒液中分离出树眼镜蛇利钠肽（DNP），并从人尿中分离出尿钠素。这些肽在结构上相似，均由一个17个氨基酸的核心环和一个半胱氨酸桥组成。ANP和BNP均与在心脏和其他器官中表达的利钠肽受体A（NPR-A）结合。NPR-A的激活会导致环磷酸鸟苷增加，从而介导利钠作用、抑制肾素和醛固酮，以及血管舒张、抗纤维化、抗肥厚和变时性舒张作用。因此，NP系统是心力衰竭时对抗神经体液激活的重要代偿机制。这为在外源性NP治疗急性失代偿性心力衰竭中应用提供了有力依据。本文综述了NP在急性心力衰竭综合征中的治疗应用。讨论了新兴的治疗药物和未来研究领域。
