The vagal involvement in the antiarrhythmic and arrhythmogenic effects of prostaglandin F2 alpha on ouabain-induced cardiac arrhythmias in cats

The effects of prostaglandin F2 alpha (PGF2 alpha) on ouabain-induced cardiac arrhythmias were investigated in chloralose-anaesthetized cats. Bilateral vagotomy and atropine intervention were employed to elucidate the involvement of vagal neural influences. PGF2 alpha (2-16 micrograms/kg i.v. bolus) predominantly suppressed the ouabain-induced ventricular and supraventricular arrhythmias and less commonly aggravated them in vagi-intact cats. The antiarrhythmic effect of PGF2 alpha was considerably, but not statistically significantly, decreased while its arrhythmogenic effect was significantly (p less than 0.05) increased in atropine-pretreated group. In vagotomised group PGF2 alpha failed to abolish the arrhythmias but it aggravated them to a degree comparable to that observed in vagi-intact group. It is concluded that the PGF2 alpha exhibits both antiarrhythmic and arrhythmogenic properties and these are largely due to elicitation of two opposing neural reflexes - one being protective and another being deleterious to ouabain-induced arrhythmias.     

Somatostatin as a modulator of vagal effects on heart rhythm]

In 11 experiments on anesthetised cats burst stimulation of peripheral cut end of right vagus nerve leads to synchronization of cardiac and vagus rhythms. Alterations of burst sequence frequency within definite limits has been synchronously reproduced by heart thus creating managed bradycardia possibility. Somatostatin (10(-8)-10(-9) M intravenously) decreases heart rate and inhibits total vagus chronotropic effect. Vagolytic effect of somatostatin caused a decrease of tonic component of the vagus chronotropic effect. On the other hand, somatostatin augmented the extent of the vagal synchronizing influences and caused enlargement of the ranges of managed bradycardia. The observed results testify to participation of the peptidergic mechanisms in genesis of vagal managed bradycardia.     

Gastric effects of thyrotropin-releasing hormone microinjected into the dorsal vagal nucleus in cats

We investigated the gastric acid secretory and motility responses to microinjection of thyrotropin-releasing hormone (TRH) into the dorsal motor nucleus of the vagus (DMV) in anesthetized cats. Gastric acid output was collected every 15 min through a gastric cannula after saline flush and titrated to pH 7.0. Antral and corpus contractions were continuously recorded by extraluminal force transducers. TRH dissolved in 200 nl of saline and microinjected unilaterally into the DMV induced a dose-dependent (50-200 ng) increase in gastric acid secretion. The acid secretory response began in the first 15 min collection and lasted 45 min. TRH frequently increased the force of contractions of the antrum and corpus within one minute of microinjection. The minimal effective dose for eliciting increased motility was lower than for inducing acid secretion. These results demonstrate that TRH acts in the DMV of cats to stimulate gastric acid secretion and contractions.     

Inhibitory effects of beta-alanine on the vagal efferent and afferent excitatory responses of the stomach to stimulation of vagal trunk in cats.

The effects of beta-alanine on the electrically evoked vagal efferent (hexamethonium-sensitive initial excitatory response) and afferent (hexamethonium-resistant delayed excitatory response) responses of the cat stomach were studied. beta-alanine (30 to 300 micrograms/kg, i.v.) dose-dependently inhibited both the efferent and afferent response. The IC50 values of beta-alanine on the efferent and afferent response were 296 +/- 65 micrograms/kg and 128 +/- 35 microgram/kg, respectively. Maximal inhibitory effects of beta-alanine (300 micrograms/kg, i.v.) appeared about 1 hr after the injection. Glycine and taurine (100 to 10,000 micrograms/kg) did not affect these responses. Treatment with hexamethonium (10 mg/kg, i.v.) prevented the efferent response, but augmented the afferent response. The treatment with hexamethonium abolished the inhibitory effect of beta-alanine on the afferent response. Both picrotoxin (100 and 500 micrograms/kg, i.v.) and bicuculline (2000 micrograms/kg, i.v.) antagonized the inhibitory effects of beta-alanine on the vagal efferent and afferent responses of the stomach. The present experiments clearly demonstrated that beta-alanine inhibited both the vagal efferent and afferent excitatory responses of stomach to electrical stimulation of vagal trunk in cats.     

Dynamics of the vagus effect on the cardiac rhythm during blockade of various subtypes of M-cholinoreceptors in cats

While single vagus bursts were used in cats with an incremental time delay following P-wave of the ECG, two zones were identified within the cardiac cycle differing from each other by their chronotropic responses. At the initial (approximately 120-130 ms) part of the cardiac cycle, an increase in the P-stimulus interval evoked a "moderate" (+8-16%) increment of the chronotropic response up to its maximal amplitude. Further increase of that interval provoked an "abrupt" (-80-90%) decrease of the vagus response. Block of M1-(pirenzepine), M2-(metoctramine and gallamine) or M3-(DAMP) cholinoreceptors diminished vagally-induced minimal and maximal prolongation of the ECG P-P interval and decreased the amplitude of its alterations associated with varying the position of vagus stimulus within the cardiac cycle. The coefficient delineating magnitude of the vagus effect over a zone with "moderate" changes of the chronotropic response was decreased after blocking the M1- and M2-cholinoreceptors, whereas duration of that zone was shortened following blockade of the M1- and M3-receptors. Velocity of the original vagus response and the rate of its subsequent decline decreased following blockade of the M1- and M2-subtypes of cholinoreceptors.     

Peptidergic modulation of the vagal effect on heart rhythm]

In 20 experiments on anesthetised cats burst stimulation of peripheral cut end of right vagus nerve leads to synchronisation of cardiac and vagus rhythms. Inhibitory effect of dalargin was caused by a decrease of tonic component while secretin would selectively inhibit synchronizing component. The observed results testify to existence of selective peptidergic modulation of vagus influence on the cardiac rhythm.     

Assessment of the reflex vagal origin of broncho-constrictor effects of hypercapnia in cats (author's transl)

Breath-by-breath measurements of pulmonary resistance (RL) were used to study the bronchomotor effects produced by the inhalation of a CO2-enriched gas mixture in anaesthetized, spontaneously breathing cats. A significant increase in RL occurred from the second inhalation of the hypercapnic gas mixture. This bronchoconstrictor effect lasted about 18 seconds, then a marked decrease in RL was observed. The secondary bronchodilatation persisted during the entire hypercapnic test (4 min). After surgical suppression of the sensory vagal component at the level of the nodose ganglion (bilateral sensory vagotomy), the early bronchoconstrictor effect of CO2 disappeared, but the secondary bronchodilatation was unchanged. In other experiments, after procaine block of the nervous conduction in non-myelinated vagal fibers, the bronchomotor effects of CO2 were the same as those observed after sensory vagotomy. In contrast, an electrotonic block of both vagus nerves, which abolished nervous conduction in myelinated fibers, did not suppress the bronchoconstrictor response to hypercapnia. Thus, the early increase in RL, which follows inhalation of a hypercapnic gas mixture, seems to be reflexly mediated by vagal afferents, especially by non-myelinated fibers.     

Paradoxical effects of chemicals in the diet on health

In 1992, Block et al. published a summary of 200 epidemiological investigations which indicated that a diet that was high in fruit and vegetables cut cancer risks approximately in half. These investigations used conventionally farmed produce that contained traces of synthetic pesticides and mycotoxins as well as an estimated 10,000 secondary products (i.e. natural pesticides). Dietary consumption of fruits and vegetables also reduces risks of cardiovascular disease, cataracts and brain dysfunction. Before genetic manipulation is undertaken to elevate or diminish any individual constituent of fruits and vegetables, the contribution of each of these constituents to health must be better understood, as in many cases their effects on health can be paradoxical.     

Increased vagal tone in adaptation to the effects of continuous stress and termination of cardiac arrhythmias

It was established in experiments on rats exposed to 5 day stress that 1 day stress resulted in a twofold decreased heart fibrillation threshold (HFT) and 5 day stress resulted in bradycardia and in the restoration of HFT to the control level. The restoration of the heart electric stability was due to an increased vagal tone because atropine eliminated the bradycardia and reduced HFT again. Adaptation to continuous 5 day stress increased 3-7-fold the heart resistance to ischemic and reperfusion arrhythmias. This protective effect was completely abolished with atropine. Thus adaptation to continuous mild stress has a potent antiarrhythmic effect which occurs due to the increased vagal tone.     

Peptide YY reduces effects of sympathetic nerves and neuropeptide Y on cardiac vagal action.

In anesthetized dogs intravenous injection of neuropeptide Y (NPY) or stimulation of the cardiac sympathetic nerve is followed by a period of attenuation of vagal action at the heart lasting from many minutes to over an hour. Peptide YY (PYY), a related peptide (but one not reported to occur in the heart or its autonomic innervation), also inhibits cardiac vagal action but is more powerful and has a longer duration action. In 5 of 9 dogs, cardiac sympathetic nerve stimulation inhibited vagal action on the heart in control conditions, but relieved preexisting inhibition when repeated in the presence of PYY. In 3 dogs, exogenous NPY inhibited cardiac vagal action in control conditions, but failed to augment preexisting inhibition in the presence of PYY. An explanation offered for these results is that when PYY is occupying receptors on vagal nerve terminals, nerve-released NPY or exogenous NPY is either unable to produce an effect, because it cannot gain access to the receptors, or displaces PYY from at least some receptors and, being less powerful than PYY in its inhibitory action, lessens the preexisting vagal attenuation. The results reported are consistent with the proposal that the factor released from the sympathetic nerves following their stimulation and which is responsible for cardiac vagal inhibition is NPY.     

Effects of high-frequency artificial respiration on the rhythm of heart contraction in cats

High-frequency artificial hyperventilation of cat lung with a rate above the initial rhythm of the heart reconstructs the rhythm so that each breathing cycle coincides with one systole of the heart. Synchronization of breathing movements and heart systoles is easily removed by atropine, and cold blockade of vagus nerves by open artificial pneumothorax.     

迷走神经对心室功能的调控机制研究进展

自主神经系统由交感神经系统和副交感神经系统（迷走神经）组成,二者相互拮抗,对哺乳动物心脏的功能调控具有重要的作用。副交感（迷走）神经对心房可产生变时、变传导和变力作用,但是对心室的支配及对心室的调控作用还不清楚。一直以来都存在一个误解,认为交感神经支配心脏的各个部位而副交感神经仅支配心脏的室上性组织,对心室没有支配。近年来的研究显示在一些哺乳动物的心脏上,胆碱能神经在心室也有分布,且对左心室的功能有重要的调控作用。本文从解剖及组织化学、分子生物学和功能学三个方面阐述迷走神经对心室的支配及调控证据,并对心章收缩功能的迷走神经（毒蕈碱）调控及其信号转导途径进行综述。     

Paradoxical effects of temperature on vascular tone

Temperature may have significant influence on vascular tone in such cases as organ preservation, coronary bypass surgery, and extracorporeal circulation. The aim of this research was to study the direct effect of temperature variation on vascular tone in an attempt to elucidate the mechanisms involved. In a first series of experiments, the isometric tension of two different vessels (rat thoracic aorta and pig renal branch artery) was studied at different temperatures. To study the role of calcium in this response, a second series of experiments was performed. In this the vessels were incubated with the intracellular chelator BAPTA/AM. Further experiments were performed to test the effect of cold storage. Our results show that changes in temperature lead to different results in pig renal artery and rat aorta. A decrease in temperature induced a highly reproducible relaxation in rat aorta, whereas pig renal artery presented cooling-induced contraction. Moreover, whereas calcium depletion failed to inhibit cooling-induced relaxation in rat aorta, it did not provoke cooling-induced contraction in pig renal artery. Similar responses were obtained with cold storage and calcium depletion. We intend to demonstrate that, just as the effect of temperature variation on pig renal artery is due to a metabolic mechanism, its effect on rat aorta may be due to structural factors. This hypothesis is supported by the result of histological studies which demonstrate a higher proportion of elastin fibres in rat aorta than in pig renal artery.     

Paradoxical effects of adenosine on neutrophil chemotaxis

Chemotaxis of rabbit neutrophils is most sensitive to inhibition by 3-deazaadenosine, followed by 3-deaza-(+/-)aristeromycin, 3-deaza-(+/-)aristeromycinylhomocysteine, 3-deazaadenosylhomocysteine, and adenosylhomocysteine, in that order. Although adenosine by itself had no effect on the chemotaxis of neutrophils, it essentially abolished the inhibitory effects of 3-deaza-adenosine on chemotaxis and the reduction of nitroblue tetrazolium. Paradoxically, adenosine enhanced the inhibition of chemotaxis by 3-deazaadenosylhomocysteine slightly and that of 3-deaza-(+/-)aristeromycin significantly. Adenosine alone unexpectedly inhibited phospholipid methylation to the same extent as 3-deazaadenosine, and reduced protein carboxymethylation to a lesser degree. The inhibition of these two methylation reactions by 3-deazaadenosine was, however, not substantially altered in the presence of adenosine. Drastic changes in the ratio of adenosylmethionine/nucleosidylhomocysteine were observed in the presence of adenosine, 3-deazaadenosine, 3-deaza-(+/-)aristeromycin, or of adenosine in combination with each of the latter compounds. There was no significant effect on the binding of chemotactic peptide to receptors, or on the ratio of ATP/ADP in cells treated by the analogs. These results suggest that the inhibition of methylation reactions per se is not enough to account for the inhibition of both chemotaxis and the reduction of nitroblue tetrazolium by neutrophils.