Attenuation of the responses to repeated cholinergic interventions in the isolated dog atrium

1986 ◽  
Vol 64 (2) ◽  
pp. 206-212 ◽  
Author(s):  
Yasuyuki Furukawa ◽  
Paul Martin

In the isolated, blood-perfused canine right atrium, which was pretreated with propranolol, negative chronotropic and inotropic responses were evoked by stimulation of the intramural parasympathetic nerve fibers or by intra-arterial infusion of acetylcholine (ACh). Successive cholinergic interventions were applied; first, a conditioning intervention for 2 min was given, then this was followed by a test intervention for 4 min. The two interventions were separated by a rest period that varied from 15 to 240 s. The cardiac responses to the conditioning parasympathetic nerve stimulation quickly reached maximum levels, and then they "faded" or progressively diminished back toward the control level. The inotropic responses to the conditioning infusion of ACh (1 μg/min) faded slightly but the chronotropic response did not. After the rest period, the test nerve stimulation evoked responses that also gradually faded with time. The maximal amplitude of the responses to the test simuli were less than those to the conditioning stimuli. This reduction in the maximal amplitude of the cardiac responses to the test stimuli was more pronounced with high frequency stimulation (30 Hz) than with low frequency stimulation (5 Hz). The decrement was also more pronounced the shorter the rest period, and it was greater at earlier times after beginning the stimulation. Conversely, the maximal cardiac responses to test infusions of ACh were not appreciably less than the responses to the conditioning infusions. We conclude, therefore, that the diminution of the cardiac responses to the second test stimulation of the parasympathetic nerve fibers was mainly ascribable to a prejunctional rather than to a postjunctional mechanism.

1984 ◽  
Vol 62 (5) ◽  
pp. 524-530 ◽  
Author(s):  
Yasuyuki Furukawa ◽  
Paul Martin ◽  
Matthew N. Levy

In the isolated, blood-perfused, canine right atrium, intramural parasympathetic nerve stimulation and intra-arterial infusions of acetylcholine induced substantial negative chronotropic and inotropic responses. The responses to parasympathetic stimulation reached their maximum values quickly, and then usually faded back toward control levels over the next 1 or 2 min of stimulation. The fade of the responses at high stimulation frequencies (≥30 Hz) was significantly greater than that at lower frequencies. The inotropic responses to acetylcholine infusion (1 μg/min) faded slightly but significantly, whereas the chronotropic responses did not fade at all. These results suggest that the fade of the cardiac responses to parasympathetic stimulation is mainly ascribable to a progressive reduction in the rate of acetylcholine release from the nerve endings, especially at higher stimulation frequencies. The fade of the inotropic responses was more pronounced and had a longer time course than that of the chronotropic responses. Furthermore, the fade of the inotropic responses diminished significantly as the response magnitude was augmented by an increase in stimulation voltage. Conversely, the fade of chronotropic responses was not significantly affected by this intervention. These differences in the inotropic and chronotropic responses to neural stimulation, and the occurrence of a slight fade of the inotropic response to acetylcholine infusion, suggest that in addition to the predominant prejunctional mechanism, a postjunctional phenomenon may also be partly responsible for the fade of the inotropic response to cholinergic interventions.


1981 ◽  
Vol 240 (4) ◽  
pp. H505-H510
Author(s):  
N. M. Buckley ◽  
P. Brazeau ◽  
I. D. Frasier ◽  
P. M. Gootman

The maturation of femoral circulatory responses to efferent lumbar nerve stimulation was tested in 51 developing swine (1 day-3 mo old) under pentobarbital sodium anesthesia (10-30 mg/kg). Aortic pressure, heart rate, and femoral and carotid arterial flows (measured by electromagnetic flow transducers) were recorded simultaneously. Femoral vascular resistance was calculated as mean aortic pressure/mean flow. Transection of the lumbar nerve fibers below the last ganglion in the sympathetic chain did not after femoral resistance in day-old animals but decreased femoral resistance in swine 1 wk of age and older. Efferent lumbar nerve stimulation at various combinations of frequencies and intensities revealed an atropine-blockable vasodilator component in the femoral circulatory response in swine 1 mo of age and older. After alpha-adrenergic receptor blockade with phentolamine (0.25 or 0.5 mg/kg), femoral vasodilation occurred during low-frequency and -intensity stimulation of the lumbar nerve only in animals 1 mo of age and older. Acetylcholine (2 micrograms ia) caused a decrease in femoral resistance at all ages. Vasoconstrictor effects of high-frequency stimulation (5-10 Hz) were present at all ages and were age dependent. The results of these experiments suggest that the femoral circulation in swine at birth in innervated by functionally active vasoconstrictor fibers, which do not provide a tonic influence on femoral resistance until late in the first postnatal week. Furthermore, although femoral vascular cholinergic receptors are demonstrable at birth, there appears to be a delay in the maturation of functionally active vasodilator fibers.


1982 ◽  
Vol 243 (2) ◽  
pp. H219-H225 ◽  
Author(s):  
P. Martin ◽  
M. N. Levy ◽  
Y. Matsuda

We applied trains of stimuli to the vagosympathetic trunks of anesthetized dogs and studied the time courses of the resultant chronotropic and inotropic responses. These responses were maximum soon after the onset of the test stimulus train but then declined over the next 1-5 min despite continued stimulation. The fade ratio was defined as the magnitude of this decline divided by the magnitude of the maximum response. For both inotropic and chronotropic responses, maximum increased with stimulation frequency, but the fade ratio did not change. In some experiments, conditioning stimulus trains of variable duration were applied before a standard rest period, after which the test stimulus train was applied. The longer the conditioning period, the lower was the subsequent fade ratio of the inotropic responses to the test stimulation train. In other experiments, a conditioning train of 2 min was applied, and then variable rest periods were interposed before the test train was applied. The longer the rest period, the greater were the subsequent maximum and fade ratios of the inotropic responses to the test stimulus train. These results indicate that some factor persists well after the cardiac responses to a given stimulus, and this factor affects the next response to an identical vagal stimulation. The chronotropic responses faded about three times faster than the inotropic responses. Thus different mechanisms may account for the fade of the inotropic and chronotropic responses.


1990 ◽  
Vol 258 (4) ◽  
pp. H1112-H1118 ◽  
Author(s):  
Y. Furukawa ◽  
D. W. Wallick ◽  
M. D. Carlson ◽  
P. J. Martin

We stimulated regional intracardiac parasympathetic nerve fibers to the atrioventricular (AV) nodal area (AVP stimuli) or to the sinoatrial (SA) nodal area (SAP stimuli) in autonomically decentralized, anesthetized dogs. AVP stimuli increased the AV interval (AV conduction time); the magnitude of the response depended directly on the stimulation frequency. AVP stimuli did not alter the atrial interval (heart period) in spontaneously beating hearts. The magnitude of the negative dromotropic response increased when the atrial interval was shortened. SAP stimuli increased the atrial interval, and the magnitude of the response depended directly on the stimulation frequency. SAP stimuli evoked little or no change in the AV interval in the unpaced heart. When the atrium was paced, SAP stimuli did not change the AV interval in about half of the preparations, and there was a small but significant change in the remaining preparations. The negative dromotropic or chronotropic response to AVP or SAP stimuli was potentiated by physostigmine and blocked by atropine. These results suggest that 1) AVP stimuli induce a selective negative dromotropic response, and 2) this negative dromotropic effect is secondarily affected by heart period, by the pacemaking site, and by atrial activation patterns, but it does not affect the sinus cycle length in the dog heart.


2000 ◽  
Vol 85 (3) ◽  
pp. 281-286 ◽  
Author(s):  
G. H. Carpenter ◽  
G. B. Proctor ◽  
L. C. Anderson ◽  
X. S. Zhang ◽  
J. R. Garrett

1990 ◽  
Vol 10 (3) ◽  
pp. 383-391 ◽  
Author(s):  
Norihiro Suzuki ◽  
Jan Erik Hardebo ◽  
Jan Kåhrström ◽  
Christer Owman

Recently, the origins and pathways of cerebrovascular acetylcholine- and vasoactive intestinal polypeptide-containing nerves have been elucidated in detail in the rat: The sphenopalatine ganglion is the major source for postganglionic parasympathetic fibers to the vascular beds of the cerebral hemispheres. To clarify the functional role of the nerves on cerebral blood vessels in vivo, brain cortical microvascular blood flow was measured in rats during electrical stimulation of these particular postganglionic fibers. Animals were subjected to transection of the right nasociliary nerve 2 weeks before the flow measurements to eliminate activation of peptidergic sensory fibers. Relative change in microvascular blood flow was continuously recorded by a laser-Doppler flowmeter system under α-chloralose anesthesia. The postganglionic fibers were electrically stimulated just proximal to the ethmoidal foramen by a bipolar platinum electrode (5 V; 0.5 ms; 3, 10, 30, 60 Hz; as a continuous stimulation for 90 s). Stimulation at 10 Hz induced a marked increase of the cortical blood flow (CoBF) on the ipsilateral side, whereas no change was observed on the contralateral side. It reached a maximum mean value of 42.5% at 46 s, and then slightly declined during the remaining stimulation period. No significant changes were observed in the mean arterial blood pressure or blood gases during or after stimulation. Both atropine and scopolamine failed to alter this flow increase. Electrical stimulation of the postganglionic fibers at different frequencies revealed a maximal increase in the CoBF at 30 Hz in the control situation (47.2%), but at 10 Hz after scopolamine administration (51.6%). This provides the first report showing that selective postganglionic stimulation of the parasympathetic nerve fibers markedly enhances blood flow in the brain, and it supports the view that the neurogenic vasodilatation is primarily noncholinergic.


1990 ◽  
Vol 267 (2) ◽  
pp. 545-548 ◽  
Author(s):  
Y Watanabe ◽  
A Takahashi ◽  
T Shimazu

The effects of sympathetic- and parasympathetic-nerve stimulation on the synthesis of transferrin and other serum proteins from [14C]leucine and their secretion were studied in rat liver perfused in situ. The radioactivities incorporated into perfusate transferrin, albumin and total protein increased with time during 90 min perfusion after an initial lag period of 15-30 min. The increases in the radioactivities of the perfusate proteins were inhibited by electrical stimulation of the hepatic nerve, whereas the increases were enhanced by vagal-nerve stimulation. Measurement of the incorporation of [14C]leucine into transferrin in the microsomal and cytosol fractions of the liver after 90 min perfusion revealed that the synthesis of this serum protein was suppressed by hepatic-nerve stimulation and increased by vagal-nerve stimulation. The results indicate that the biosynthesis and secretion of transferrin, and possibly other serum proteins, are inhibited by sympathetic-nerve stimulation and enhanced by parasympathetic-nerve stimulation.


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