title: Effects of natriuretic peptides on electrical conduction in the sinoatrial node and atrial myocardium of the heart.
abstract: 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.
authors.affiliation: 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. robert.rose@dal.ca.
authors.forename: John
authors.initials: J
authors.lastname: Azer
authors.forename: Rui
authors.initials: R
authors.lastname: Hua
authors.forename: Pooja S
authors.initials: PS
authors.lastname: Krishnaswamy
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rose
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D016275:Atrial Function / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism*; D009431:Neural Conduction / Q000502:physiology; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D012849:Sinoatrial Node / Q000502:physiology*
chemical_list: D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D017461:Receptors, Atrial Natriuretic Factor