Atrial natriuretic factor alters autonomic interactions in the control of heart rate in conscious rats

Abstract

Regulation of heart rate was studied in rats receiving either i.v. saline at 64 microL/min or synthetic 28-residue rat atrial natriuretic peptide (ANF) at a dose sufficient to decrease mean arterial blood pressure by 10%. Autonomic influences were deduced from steady-state heart rate responses of each group to propranolol, atropine, or propranolol and atropine combined. A multiplicative model of heart rate control was used to derive quantitatively from the data the modulation of intrinsic heart rate by sympathetic and parasympathetic mechanisms. Animals receiving ANF showed a lower heart rate than control animals. This relative bradycardia was abolished by atropine. Blocking of sympathetic effects with propranolol had no effect on basal heart rate in either group, and atropinization led to significant increases in heart rate in both groups of rats. Mathematical analysis of the results showed that the bradycardia produced by ANF was due predominantly to a reduced intrinsic heart rate and to enhanced vagal inhibition of postganglionic sympathetic activity. Parasympathetic contribution to heart rate in the absence of sympathetic activity was negligible in control rats and small during ANF. We conclude that the major influences of ANF on heart rate control are a decrease of intrinsic heart rate and enhanced parasympathetic inhibition of postganglionic presynaptic sympathetic activity.

Atrial Natriuretic Peptide Has Dose‐Dependent, Autonomically Mediated Effects on Atrial Refractoriness and Repolarization in Anesthetized Dogs

“…1,2,[6][7][8][9] At the organ and whole animal level, ANP has dose-dependent, modulating effects on the autonomic nervous system. 2,[10][11][12][13][14][15][16][17][18][19][20] These and other observations suggest that ANP may alter electrophysiological properties of the in vivo heart and possibly have a role in arrhythmogenesis. However, previous studies that examined ANP's electrophysiological effects at the whole heart or tissue level found This study was supported by the Department of Veterans Affairs Merit Review Award to Bruce Stambler.…”

“…ANP also acts directly at the cellular level to alter cardiac electrophysiology inhibiting L‐type Ca 2+ channels and reducing cytosolic Ca 2+ concentration in atrial and ventricular cells 1,2,6–9 . At the organ and whole animal level, ANP has dose‐dependent, modulating effects on the autonomic nervous system 2,10–20 . These and other observations suggest that ANP may alter electrophysiological properties of the in vivo heart and possibly have a role in arrhythmogenesis.…”

Cyclic nucleotide regulation of cardiac sympatho‐vagal responsiveness

“…) and rats (Ackermann et al . ) in vivo . This might be due to cross‐talk between adrenergic and cholinergic receptors on parasympathetic ganglia, since the effect of ANP can be blocked by an α 1 ‐antagonist (Atchison & Ackermann, ).…”

Severe hypotension and bradycardia after continuous intravenous infusion of urodilatin (ANP 95–126) in a patient with congestive heart failure

“…The related peptide ANP(99-126) exhibits sym- pathoinhibitory activity [4,5], which may be due to central or ganglionic actions [6], but post-ganglionic effects on adrenergic, cardiac and vascular sympathetic nerve endings have also been described [7,8].…”