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.

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.

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.

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]

Effect of vasoactive intestinal peptide on pacemaker location and heart rate in the dog atrium

1998 ◽  
Vol 76 (4) ◽  
pp. 457-462 ◽  
Author(s):  
Arnold Pintér ◽  
Réginald Nadeau ◽  
Nazih Dandan ◽  
Pierre L Pagé
Keyword(s):  
Heart Rate ◽  
Vasoactive Intestinal Peptide ◽  
Sinus Node ◽  
Sinus Node Artery ◽  
Anesthetized Dogs ◽  
Similar Decrease ◽  
Intravenous Sodium ◽  
Unipolar Electrograms ◽  
Positive Chronotropic Effect ◽  
Atrial Mapping

Vasoactive intestinal polypeptide (VIP) was either injectedintravenously (300 pmol·kg–1) or perfused (1 nmol in 1 min) into the sinusnode artery (SNA) in anesthetized dogs to study its effect on subsidiary atrial pacemakers.Isochronal maps were obtained from 128 unipolar electrograms recorded on the epicardialsurface of both atria in nine animals. When VIP was perfused into the SNA or injectedintravenously, heart rate increased by 29 ± 16% and 12 ± 12%, and blood pressure decreased by16 ± 15 mmHg (1 mmHg = 133.3 Pa) and 24 ± 18 mmHg, respectively. Nosignificant change in heart rate (3 ± 6% decrease) accompanied a similar decrease in bloodpressure after an intravenous sodium nitroprusside perfusion. The perfusion of VIP into the SNAas well as the intravenous injection of VIP induced a shift of the pacemaker site to the region ofBachmann’s bundle in a third of the preparations, while the pacemaker remained in the sinusnode area in two thirds. A perfusion of isoproterenol into the SNA produced a similar heart rateincrease (32 ± 14%, NS vs. VIP), and shifted the pacemaker site rostrally within the sinus node inthree of five preparations, or to the region of Bachmann’s bundle in two of five preparations.The response to VIP in the location of the pacemaker was significantly different from theresponse to isoproterenol. Repeated perfusions of VIP into the SNA after 10-, 25-, 40-, and60-min intervals produced 2 ± 13% (p < 0.005 vs. the effect of first VIP administration),14 ± 12% (p < 0.05), 10 ± 12% (p < 0.05) and 30 ± 13% (NS) heart rateincreases, respectively, thereby demonstrating a tachyphylactic effect. In conclusion, VIP seemsto exert its positive chronotropic effect directly (probably via specific VIP receptors), althoughthe phenomenon of tachyphylaxis may suggest an indirect sympathomimetic mechanism.Key words: vasoactive intestinal peptide,subsidiary atrial pacemakers, sinus node artery, atrial mapping.

Autonomic control of pacemaker activity in the atrioventricular junction of the dog

1978 ◽  
Vol 235 (3) ◽  
pp. H308-H313 ◽  
Author(s):  
D. W. Wallick ◽  
D. Felder ◽  
M. N. Levy
Keyword(s):  
Sinus Node ◽  
Pacemaker Activity ◽  
Vagal Activity ◽  
Sympathetic Stimulation ◽  
Pacemaker Cells ◽  
Junctional Rhythm ◽  
Group Of Seven ◽  
Sinus Node Artery ◽  
Anesthetized Dogs ◽  
High Level

A stable atrioventricular (AV) junctional rhythm was induced in open-chest, anesthetized dogs by injecting pentobarbital into the sinus node artery. A factorial experimental design was used to quantify the changes in AV junctional rate as a function of the frequency of cardiac sympathetic and parasympathetic stimulation. The AV junctional pacemaker cells were more responsive to autonomic neural stimulation, but the vagal-sympathetic interactions were less pronounced than had previously been observed for the SA nodal pacemaker cells. In a group of seven animals, sympathetic stimulation at a frequency of 1.4 Hz increased the AV junctional rate by 102% from a control rate of 54 beats/min. In the same animals, vagal stimulation at a frequency of 8.4 Hz reduced the AV junctional rate by 56%. In three other animals, the AV junction was even more responsive; equivalent chronotropic effects were achieved with stimulation frequencies that were only about one-third of those cited above. There was a moderate, but significant, autonomic interaction: in the group of seven animals, the positive chronotropic effect of sympathetic stimulation at 1.4 Hz was 72% greater at the low level (0 Hz) than at the high level (8.4 Hz) of vagal activity.

Exercise training and responsiveness of isolated coronary arteries

1991 ◽  
Vol 71 (6) ◽  
pp. 2346-2351 ◽  
Author(s):  
P. J. Rogers ◽  
T. D. Miller ◽  
B. A. Bauer ◽  
J. M. Brum ◽  
A. A. Bove ◽  
...  
Keyword(s):  
Exercise Training ◽  
Coronary Arteries ◽  
Vasoactive Intestinal Polypeptide ◽  
Adrenergic Agonists ◽  
Response Curves ◽  
Beta Adrenergic ◽  
Beta Adrenergic Agonists ◽  
The Right ◽  
Intestinal Polypeptide

Exercise is associated with release of catecholamines and vasoactive intestinal polypeptides. Recurrent exposure to catecholamines modifies the sensitivity of adrenoceptors. To test the hypothesis that exercise training may affect the sensitivity of the epicardial coronary arteries, we performed studies on isolated coronary arteries from male dogs capable of running on a treadmill. The animals were separated randomly into two groups: sedentary and exercise training. After 11 wk, rings of left circumflex and left anterior descending coronary arteries were studied in vitro. Contractions to alpha 1-adrenergic agonists (norepinephrine and phenylephrine) were not affected by exercise training. During contractions with prostaglandin F2 alpha, endothelium-dependent relaxations to alpha 2-adrenergic agonists (norepinephrine and UK 14304) were not reduced significantly by exercise training. The concentration-relaxation curves to beta-adrenergic agonists (norepinephrine, isoproterenol, and epinephrine) were shifted to the right after training. The concentration-response curves to vasoactive intestinal polypeptide, but not that to substance P, were shifted to the right in rings with endothelium from exercise-trained animals. These findings demonstrate a decrease in responsiveness of canine vascular smooth muscle to beta-adrenergic agonists and to vasoactive intestinal polypeptide after exercise training.

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