Azer John, Hua Rui, Krishnaswamy Pooja S, Rose Robert A
Department of Physiology and Biophysics, Dalhousie University, Sir Charles Tupper Medical Building - Room 4J, 5850 College Street, PO Box 15000, Halifax, Nova Scotia, Canada, B3H 4R2.
J Physiol. 2014 Mar 1;592(5):1025-45. doi: 10.1113/jphysiol.2013.265405. Epub 2013 Dec 16.
Natriuretic peptides, including B-type and C-type natriuretic peptide (BNP and CNP), are powerful regulators of the cardiovascular system; however, their electrophysiological effects in the heart, particularly in the sinoatrial node (SAN), are incompletely understood. We have used high-resolution optical mapping to measure the effects of BNP and CNP, and the roles of natriuretic peptide receptors (NPR-A, NPR-B and NPR-C), on electrical conduction within the SAN and atrial myocardium. In basal conditions BNP and CNP (50-500 nm) increased conduction velocity (CV) within the SAN by ∼30% at the high dose and shifted the initial exit site superiorly. These effects sped conduction from the SAN to the surrounding atrial myocardium and were mediated by the NPR-A and NPR-B receptors. In the presence of isoproterenol (1 μm) the NPR-C receptor made a major contribution to the effects of BNP and CNP in the heart. In these conditions BNP, CNP and the NPR-C agonist cANF each decreased SAN CV and shifted the initial exit site inferiorly. The effects of cANF (30% reduction) were larger than BNP or CNP (∼15% reduction), indicating that BNP and CNP activate multiple natriuretic peptide receptors. In support of this, the inhibitory effects of BNP were absent in NPR-C knockout mice, where BNP instead elicited a further increase (∼25%) in CV. Measurements in externally paced atrial preparations demonstrate that the effects of natriuretic peptides on CV are partially independent of changes in cycle length. These data provide detailed novel insight into the complex effects of natriuretic peptides and their receptors on electrical conduction in the heart.
利钠肽，包括B型利钠肽和C型利钠肽（BNP和CNP），是心血管系统的强大调节因子；然而，它们在心脏，尤其是在窦房结（SAN）中的电生理作用尚未完全明确。我们使用高分辨率光学映射技术来测量BNP和CNP的作用，以及利钠肽受体（NPR-A、NPR-B和NPR-C）在SAN和心房心肌电传导中的作用。在基础条件下，高剂量的BNP和CNP（50 - 500 nM）使SAN内的传导速度（CV）增加约30%，并使初始出口位点向上移动。这些作用加速了从SAN到周围心房心肌的传导，并且由NPR-A和NPR-B受体介导。在异丙肾上腺素（1 μM）存在的情况下，NPR-C受体对BNP和CNP在心脏中的作用起主要作用。在这些条件下，BNP、CNP和NPR-C激动剂cANF均降低了SAN的CV，并使初始出口位点向下移动。cANF的作用（降低30%）大于BNP或CNP（降低约15%），表明BNP和CNP激活多种利钠肽受体。支持这一点的是，在NPR-C基因敲除小鼠中不存在BNP的抑制作用，在这种情况下BNP反而使CV进一步增加（约25%）。在外部起搏的心房标本中的测量表明，利钠肽对CV的作用部分独立于心动周期长度的变化。这些数据为利钠肽及其受体对心脏电传导的复杂作用提供了详细的新见解。
