Department of Cardiovascular Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
Pharmacol Ther. 2021 Nov;227:107863. doi: 10.1016/j.pharmthera.2021.107863. Epub 2021 Apr 21.
Natriuretic peptides, which are activated in heart failure, play an important cardioprotective role. The most notable of the cardioprotective natriuretic peptides are atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which are abundantly expressed and secreted in the atrium and ventricles, respectively, and C-type natriuretic peptide (CNP), which is expressed mainly in the vasculature, central nervous system, and bone. ANP and BNP exhibit antagonistic effects against angiotensin II via diuretic/natriuretic actions, vasodilatory actions, and inhibition of aldosterone secretion, whereas CNP is involved in the regulation of vascular tone and blood pressure, among other roles. ANP and BNP are of particular interest with respect to heart failure, as their levels, most notably BNP and N-terminal proBNP-a cleavage product produced when proBNP is processed to mature BNP-are increased in patients with heart failure. Furthermore, the identification of natriuretic peptides as sensitive markers of cardiac load has driven significant research into their physiological roles in cardiovascular homeostasis and disease, as well as their potential use as both biomarkers and therapeutics. In this review, I discuss the physiological functions of the natriuretic peptide family, with a particular focus on the basic research that has led to our current understanding of its roles in maintaining cardiovascular homeostasis, and the pathophysiological implications for the onset and progression of heart failure. The clinical significance and potential of natriuretic peptides as diagnostic and/or therapeutic agents are also discussed.
利钠肽在心力衰竭中被激活,发挥着重要的心脏保护作用。其中,最显著的心脏保护利钠肽包括心房利钠肽(ANP)和脑利钠肽(BNP),它们分别在心房和心室中大量表达和分泌,而 C 型利钠肽(CNP)主要在血管、中枢神经系统和骨骼中表达。ANP 和 BNP 通过利尿/利钠作用、血管扩张作用和抑制醛固酮分泌对血管紧张素 II 发挥拮抗作用,而 CNP 则参与调节血管张力和血压等作用。ANP 和 BNP 在心力衰竭方面特别引人关注,因为它们的水平,特别是心力衰竭患者中增加的 BNP 和前 BNP 加工成熟 BNP 时产生的 N-末端 proBNP-a 裂解产物,都有所增加。此外,将利钠肽鉴定为心脏负荷的敏感标志物,推动了对其在心血管稳态和疾病中的生理作用及其作为生物标志物和治疗剂的潜在用途的大量研究。在这篇综述中,我讨论了利钠肽家族的生理功能,特别关注了导致我们目前理解其在维持心血管稳态中的作用的基础研究,以及心力衰竭发病和进展的病理生理意义。还讨论了利钠肽作为诊断和/或治疗剂的临床意义和潜力。