Effects of repetitive vagal stimulation on heart rate and on cardiac vasoactive intestinal polypeptide efflux

1995 ◽  
Vol 268 (5) ◽  
pp. H1939-H1946 ◽  
Author(s):  
M. R. Hill ◽  
D. W. Wallick ◽  
P. J. Martin ◽  
M. N. Levy
Keyword(s):  
Vasoactive Intestinal Polypeptide ◽  
Vagal Stimulation ◽  
Sinus Node ◽  
Cardiac Pacemaker ◽  
Close Correlation ◽  
Right Atrial ◽  
Chronotropic Response ◽  
Sinus Node Artery ◽  
Stimulation Regimen ◽  
Intestinal Polypeptide

In dogs anesthetized with alpha-chloralose, we assessed the "vagally induced tachycardia" elicited by successive 2-min periods of intense vagal stimulation (0.5 ms, 10 mA, 20 Hz) after we had blocked the animals' muscarinic and beta-adrenergic receptors with atropine and propranolol, respectively. We found that the tachycardia produced by the successive vagal stimulations progressively decreased to < 20% of the initial tachycardia response within 84 min. We also observed that the chronotropic response to vasoactive intestinal polypeptide (VIP) injected into the sinus node artery after the vagal stimulation regimen did not differ significantly from the response to the same dose of VIP injected prior to vagal stimulation. This finding indicates that the postjunctional responsiveness of the cardiac pacemaker cells had not diminished over the course of the vagal stimulation regimen. In isolated, perfused right atrial preparations, we observed a close correlation between the efflux of VIP from the atrial tissues and the chronotropic responses to vagal stimulation. Our results support the hypotheses that 1) VIP is a mediator of vagally induced tachycardia, 2) the reduction in VIP efflux is associated with a diminished vagally induced tachycardia, and 3) the reduced efflux of VIP probably reflects a diminution in neuronal release, perhaps by depletion of this peptide from the vagus nerve endings consequent to the prolonged neural stimulation.

Vasoactive intestinal polypeptide antagonists attenuate vagally induced tachycardia in the anesthetized dog

1995 ◽  
Vol 269 (4) ◽  
pp. H1467-H1472 ◽  
Author(s):  
M. R. Hill ◽  
D. W. Wallick ◽  
L. R. Mongeon ◽  
P. J. Martin ◽  
M. N. Levy
Keyword(s):  
Vasoactive Intestinal Polypeptide ◽  
Adrenergic Receptor ◽  
Vagal Stimulation ◽  
Sinus Node ◽  
The Other ◽  
Vagus Nerves ◽  
Sinus Node Artery ◽  
Anesthetized Dogs ◽  
Intestinal Polypeptide

We used three vasoactive intestinal polypeptide (VIP) antagonists, VIP-(10-28), [p-Cl-D-Phe6,Leu17]VIP, and NT-VIP, to evaluate the role of VIP as a mediator of vagally induced tachycardia in chloralose-anesthetized dogs. After we administered muscarinic and beta-adrenergic receptor antagonists, we evoked vagally induced tachycardia either directly, by stimulating the vagus nerves for 2 min, or reflexly, by injecting phenylephrine to increase blood pressure. Furthermore, each of the antagonists attenuated the tachycardias induced by vagal stimulation by approximately 50% and the reflexly induced tachycardias by approximately 70%. Each VIP antagonist attenuated the chronotropic responses that we evoked by injecting VIP (5.2 ng/kg) into the sinus node artery. We tested the specificity of these VIP antagonists by determining whether they attenuated the increases in heart rate evoked by two other neuropeptides [peptide histidine isoleucine (PHI) and glucagon]. VIP-(10-28) attenuated the response to PHI, but not to glucagon. The other two VIP antagonists did not alter the chronotropic responses to PHI or glucagon. Our results support the hypothesis that neurally released VIP is the principal mediator of vagally induced tachycardia in the dog.

Vasoactive intestinal polypeptide enhances automaticity of supraventricular pacemakers in anesthetized dogs

1991 ◽  
Vol 261 (2) ◽  
pp. H463-H468 ◽  
Author(s):  
D. F. Rigel ◽  
D. A. Lathrop
Keyword(s):  
Vasoactive Intestinal Polypeptide ◽  
Sinus Node ◽  
Cardiac Pacemaker ◽  
Autonomic Nerve ◽  
Beta Adrenergic ◽  
Pentobarbital Sodium ◽  
Sinus Node Artery ◽  
Anesthetized Dogs ◽  
Muscarinic Cholinergic ◽  
Intestinal Polypeptide

Effects of the cardiac neuropeptide vasoactive intestinal polypeptide (VIP) and isoproterenol (ISO) were compared on sinus nodal, subsidiary atrial, and atrioventricular junctional pacemaker automaticity in pentobarbital sodium-anesthetized dogs (n = 14). Autonomic cardiac nerves were decentralized by bilateral vagotomy and stellectomy. VIP and ISO (30, 100, and 300 pmol/kg iv) were administered during sinus rhythm and either after crushing the sinus node to unmask a latent subsidiary atrial pacemaker (n = 7 dogs) or after injecting pentobarbital sodium into the sinus node artery to elicit an atrioventricular junctional pacemaker (n = 7). Spontaneous sinus nodal, subsidiary atrial, and atrioventricular junctional pacemaker rates (after autonomic nerve decentralization) were 142 +/- 4, 114 +/- 3, and 79 +/- 4 beats/min (means +/- SE), respectively. Both VIP and ISO dose dependently increased the rates of all three pacemaker sites. Combined muscarinic-cholinergic (atropine; 0.11 mg/kg iv) and beta-adrenergic receptor blockade (nadolol; 0.5 mg/kg iv) abolished the stimulatory effects of ISO on subsidiary atrial and atrioventricular junctional pacemakers but did not affect the responses to VIP. We conclude that exogenous VIP enhances the automaticity of sinus nodal, subsidiary atrial, and atrioventricular junctional pacemakers independently of muscarinic-cholinergic and beta-adrenergic receptors. Based on the previous demonstration of VIP-immunoreactive nerves throughout the heart, our findings also suggest that endogenous VIP may be involved in cardiac pacemaker regulation.

Effects of neuropeptides on heart rate in dogs: comparison of VIP, PHI, NPY, CGRP, and NT

1988 ◽  
Vol 255 (2) ◽  
pp. H311-H317 ◽  
Author(s):  
D. F. Rigel
Keyword(s):  
Heart Rate ◽  
Neuropeptide Y ◽  
Vasoactive Intestinal Polypeptide ◽  
Sinus Node ◽  
Calcitonin Gene Related Peptide ◽  
Adrenergic Blockade ◽  
Related Peptide ◽  
Sinus Node Artery ◽  
Calcitonin Gene ◽  
Intestinal Polypeptide

This study was designed to evaluate the potential chronotropic actions of several cardiac neuropeptides in pentobarbital-anesthetized dogs. After bilateral vagotomy and stellectomy and muscarinic receptor blockade, I injected vasoactive intestinal polypeptide, peptide histidine isoleucine, neuropeptide Y, neurotensin, and calcitonin gene-related peptide into the intact sinus node artery. Neurotensin, calcitonin gene-related peptide, and neuropeptide Y exhibited no physiologically significant changes in heart rate. However, the structural homologues vasoactive intestinal polypeptide and peptide histidine isoleucine each augmented heart rate with maximal increases (approximately 120 beats/min) similar to those of norepinephrine. Vasoactive intestinal polypeptide and peptide histidine isoleucine were twice and 1/18, respectively, as potent as norepinephrine. The cardioacceleratory responses to vasoactive intestinal polypeptide and peptide histidine isoleucine were more slowly developing and longer lasting than those of norepinephrine. The responses to these two peptides were unchanged after beta-adrenergic blockade with propranolol in a dose sufficient to eliminate or greatly attenuate the norepinephrine tachycardia. These results indicate a potential role of endogenous vasoactive intestinal polypeptide and peptide histidine isoleucine in nonadrenergic, noncholinergic heart rate control in the dog.

Evaluation of β-Adrenerglc Blocking Agents in Presence of Adrenergic Tone

1972 ◽  
Vol 50 (5) ◽  
pp. 381-388
Author(s):  
Victor Elharrar ◽  
Reginald A. Nadeau
Keyword(s):  
Dose Response ◽  
Sinus Node ◽  
Stellate Ganglion ◽  
Sodium Pentobarbital ◽  
Response Curves ◽  
Chronotropic Response ◽  
Blocking Agents ◽  
Sinus Node Artery ◽  
Anesthetized Dogs ◽  
The Right

The importance of the level of adrenergic tone in the determination of the dose–response curve to noradrenaline (NA) and in the evaluation of β-adrenergic blocking agents was studied in open-chest sodium pentobarbital anesthetized dogs by injecting drugs directly into the sinus node artery. Changes in the level of adrenergic tone by stimulating the right stellate ganglion resulted in variation of the observed chronotropic response to NA and of its ED50. The chronotropic responses were corrected by taking into account the underlying adrenergic tone. The negative chronotropic effect of dl-propranolol (1 and 10 μg) appeared to be related to its β-blocking properties and not to its quinidine-like effects as shown by the lack of effect of d-propranolol injected at the same doses. The magnitude of the negative chronotropic effects of 10 μg of propranolol and 100 μg of practolol, oxprenolol, and sotalol was shown to be related to the initial heart rate and consequently to the level of adrenergic tone. The comparison of these four β-blocking agents was carried out on corrected dose-response curves to NA. Their relative potencies were found to be: propranolol > oxprenolol > practolol > sotalol, corresponding to ratios of 1, [Formula: see text], [Formula: see text], and [Formula: see text]

scholarly journals Chronic atropine administration diminishes the contribution of vasoactive intestinal polypeptide to heart rate regulation

2008 ◽  
pp. 827-837
Author(s):  
J Kuncová ◽  
Š Faitová ◽  
J Capouch ◽  
M Štengl ◽  
J Slavíková
Keyword(s):  
Heart Rate ◽  
Single Dose ◽  
Vasoactive Intestinal Polypeptide ◽  
Rat Heart ◽  
Vagal Stimulation ◽  
Rate Regulation ◽  
Heart Rate Regulation ◽  
The Impact ◽  
Heart Atria ◽  
Intestinal Polypeptide

Vasoactive intestinal polypeptide (VIP) is implicated in the modulation of vagal effects on the heart rate. In this study, the impact of acute and chronic atropine administration on VIP levels in rat heart atria was investigated in relation to heart rate in the course of vagus nerves stimulation. Anaesthetised control and atropinised (10 mg/kg/day for 10 days) rats pretreated with metipranolol and phentolamine that were either given or not a single dose of atropine were subjected to bilateral vagus nerve stimulation (30 min: 0.7 mA, 20 Hz, 0.2 ms). VIP concentrations in the atria were determined after each stimulation protocol. In control rats with or without single atropine administration, the heart rate upon vagal stimulation was higher than in atropinised animals with or without single atropine dose, respectively. VIP concentrations in the control atria were significantly decreased after the stimulation; the decrease was comparable both in the absence and presence of a single dose of atropine. Compared to controls, VIP levels were significantly decreased after chronic atropine treatment and they were not further reduced by vagal stimulation and single atropine administration. Administration of VIP antagonist completely abolished the differences in the heart rate upon vagal stimulation between control and atropinised groups. In conclusion, the data indicate that chronic atropine administration affects VIP synthesis in rat heart atria and consequently it modifies the heart rate regulation.

Long-term effects of hyperpolarization-activated inward current blockade on cardiac parasympathetic activity

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
A Scridon ◽  
VB Halatiu ◽  
AI Balan ◽  
DA Cozac ◽  
GV Moldovan ◽  
...  
Keyword(s):  
Heart Rate ◽  
Vagus Nerve ◽  
Vagal Stimulation ◽  
Sinus Node ◽  
Vagal Tone ◽  
Right Atrial ◽  
The Right

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant of the Romanian Ministry of Education and Research, CNCS - UEFISCDI Background The autonomic control of the pacemaker current, If, and the molecular mechanisms underlying parasympathetic If modulation are well understood. Conversely, the effects of chronic If blockade on the parasympathetic nervous system and on the heart rate (HR) response to acute parasympathetic changes are still largely unknown. Such interactions could significantly influence the course of patients undergoing chronic therapy with the If blocker ivabradine. Purpose We aimed to assess the effects of long-term If blockade using ivabradine on cardiac autonomic modulation and on the cardiovascular response to acute in vivo and in vitro parasympathetic stimulation. Methods Radiotelemetry ECG transmitters were implanted in 6 Control and 10 ivabradine-treated male Wistar rats (IVA; 3 weeks, 10 mg/kg/day); sympathetic and parasympathetic heart rate variability parameters were assessed. At the end of the study, the right atrium was removed and right atrial HCN(1-4) RNA expression levels were analyzed. The HR and systolic blood pressure (SBP) responses to in vivo electrical stimulation of the right vagus nerve (2–20 Hz) and the spontaneous sinus node discharge rate (SNDR) response to in vitro cholinergic receptors stimulation using carbamylcholine (10-9–10-6 mol/L) were assessed in 6 additional Control and 10 IVA rats. Results At the end of the study, mean 24-h HR was significantly lower in the IVA compared with the Control rats (301.3 ± 7.5 bpm vs. 341.5 ± 8.3 bpm; p&lt; 0.01). Ivabradine administration led to a significant increase in vagal tone and shifted the sympatho-vagal balance towards vagal dominance (awake, asleep, and over 24-h; all p&lt; 0.05). In the Control rats, in vivo vagus nerve stimulation induced a progressive decrease in both the SBP (p = 0.0001) and the HR (p&lt; 0.0001). Meanwhile, in the IVA rats, vagal stimulation had no effect on the HR (p = 0.16) and induced a significantly lower drop in SBP (p&lt; 0.05). Ivabradine-treated rats also presented a significantly lower SNDR drop in response to carbamylcholine (p&lt; 0.01) and significantly higher HCN4 expression (p = 0.02). Conclusion Long-term If blockade using ivabradine caused a significant increase in vagal tone and shifted the autonomic balance towards vagal dominance in rats. Given the highly proarrhythmic effects of vagal activation at the atrial level, these findings could provide an explanation for the increased risk of atrial fibrillation associated with ivabradine use in clinical trials. In addition, ivabradine reduced the HR response to direct muscarinic receptors stimulation, canceled the cardioinhibitory response and blunted the hemodynamic response to in vivo vagal stimulation, and led to significant sinus node HCN4 up-regulation. These data suggest that ivabradine-induced HCN4 and the consequent If up-regulation could render the sinus node less sensitive to acute vagal inputs and could thus protect against excessive bradycardia induced by acute vagal activation.

Effects of repetitive bursts of vagal activity on atrioventricular junctional rate in dogs

1979 ◽  
Vol 237 (3) ◽  
pp. H275-H281 ◽  
Author(s):  
D. W. Wallick ◽  
M. N. Levy ◽  
D. S. Felder ◽  
H. Zieske
Keyword(s):  
Cardiac Cycle ◽  
Sinus Node ◽  
Critical Time ◽  
Large Change ◽  
Vagal Activity ◽  
Vagus Nerves ◽  
Pacemaker Cells ◽  
Chronotropic Response ◽  
Sinus Node Artery ◽  
The Mean

A stable atrioventricular (AV) junctional rhythm was produced in open-chest dogs by injecting pentobarbital into the sinus node artery. When the cervical vagus nerves were stimulated repetitively, the junctional pacemaker cells tended to become synchronized with the vagal activity. During such synchronization, the junctional rate varied directly rather than inversely with the frequency of vagal stimulation. The magnitude of the chronotropic response depended on the timing of the vagal stimuli within the cardiac cycle. In 9 dogs, when the mean heart periods were plotted as a function of the R-st intervals (i.e., the time from the beginning of ventricular depolarization to the beginning of the stimulus burst), the mean heart periods varied from a maximum of 1,815 ms to a minimum of 1,160 ms, depending on the R-st interval. A small change in the R-st interval was capable of evoking a relatively large change in cycle length. Therefore, the impulses from various efferent vagal fibers to the AV junction must arrive almost synchronously, the released acetylcholine must be removed rapidly, and the sensitivity of the pacemaker cells to acetylcholine must change rapidly at some critical time during the cardiac cycle.

Modulation of electrophysiological properties of neonatal canine heart by tonic parasympathetic stimulation

1990 ◽  
Vol 258 (1) ◽  
pp. H38-H44 ◽  
Author(s):  
A. S. Pickoff ◽  
A. Stolfi
Keyword(s):  
Cycle Length ◽  
Parasympathetic Nervous System ◽  
Vagal Stimulation ◽  
Sinus Node ◽  
Right Atrial ◽  
Conduction Time ◽  
Canine Heart ◽  
Electrophysiological Properties ◽  
Refractory Periods ◽  
The Right

The effects of tonic right and left vagal stimulation (RVS and LVS) on electrophysiological properties of the immature myocardium and specialized conduction system were evaluated in 11 neonatal canines pretreated with propranolol (1 mg/kg iv). Electrophysiological studies were performed by recording intracardiac electrograms from multiple endocardial catheters during programmed electrical stimulation. Assessments were made of sinus node function, intra-atrial, atrioventricular (AV) nodal and His-Purkinje conduction, and atrial and ventricular refractoriness in the control state and during RVS and LVS at 4–12 Hz. Vagal stimulation prolonged the sinus cycle length; RVS produced a 38% increase and LVS a 25% increase at 8 Hz (P less than 0.01). There were no changes in the intra-atrial or His-Purkinje conduction times. Comparable increases occurred during RVS and LVS in the paced cycle length resulting in AV nodal Wenckebach, the AV nodal conduction time at a paced cycle length of 340 ms, and the effective and functional refractory periods of the AV node, suggesting symmetrical influences of the right and left vagus on neonatal AV nodal function. Right atrial effective and functional refractory periods shortened significantly during vagal stimulation (ERP, 36% RVS and 23% LVS; FRP, 27% RVS and 15% LVS), and in 5 of 11 neonates, a sustained regular atrial tachyarrhythmia was induced during atrial extra-stimulation. Small yet significant increases were observed in the right ventricular ERP and FRP during vagal stimulation. This study provides information regarding the functional integrity of the parasympathetic nervous system and its potential role as a modulator of the electrophysiological properties of the newborn heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Sign in / Sign up

Export Citation Format

Share Document