In vivo assessment of acetylcholine-releasing function at cardiac vagal nerve terminals

Kawada, Toru; Yamazaki, Toji; Akiyama, Tsuyoshi; Shishido, Toshiaki; Inagaki, Masumi; Uemura, Kazunori; Miyamoto, Tadayoshi; Sugimachi, Masaru; Takaki, Hiroshi; Sunagawa, Kenji

doi:10.1152/ajpheart.2001.281.1.h139

Cited by 29 publications

(27 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus the magnitude of the BJ reflex could differ from that induced by myocardial ischemia. However, an increase in the myocardial acetylcholine level induced by intravenous PBG (80 g/kg) was similar to that observed in the nonischemic myocardium during coronary artery occlusion in anesthetized cats (11,12). Therefore, the extent of the BJ reflex induced by the present doses of PBG might not be far from that induced by myocardial ischemia.…”

Section: Clinical Implicationsupporting

confidence: 69%

Bezold-Jarisch reflex attenuates dynamic gain of baroreflex neural arc

Kashihara

Kawada²,

Yanagiya³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

risch reflex attenuates dynamic gain of baroreflex neural arc. Am J Physiol Heart Circ Physiol 285: H833-H840, 2003. First published April 24, 2003 10.1152/ajpheart.01082. 2002-Although acute myocardial ischemia or infarction may induce the Bezold-Jarisch (BJ) reflex through the activation of serotonin receptors on vagal afferent nerves, the mechanism by which the BJ reflex modulates the dynamic characteristics of arterial pressure (AP) regulation is unknown. The purpose of this study was to examine the effects of the BJ reflex induced by intravenous phenylbiguanide (PBG) on the dynamic characteristics of the arterial baroreflex. In seven anesthetized rabbits, we perturbed intracarotid sinus pressure (CSP) according to a white noise sequence while renal sympathetic nerve activity (RSNA), AP, and heart rate (HR) were recorded. We estimated the transfer function from CSP to RSNA (neural arc) and from RSNA to AP (peripheral arc) before and after 10 min of intravenous administration of PBG (100 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ). The intravenous PBG decreased mean AP from 84.5 Ϯ 4.0 to 68.2 Ϯ 4.7 mmHg (P Ͻ 0.01), mean RSNA to 76.2 Ϯ 7.0% (P Ͻ 0.05), and mean HR from 301.6 Ϯ 7.7 to 288.4 Ϯ 9.0 beats/min (P Ͻ 0.01). The intravenous PBG significantly decreased neural arc dynamic gain at 0.01 Hz (1.06 Ϯ 0.08 vs. 0.59 Ϯ 0.17, P Ͻ 0.05), whereas it did not affect that of the peripheral arc (1.20 Ϯ 0.12 vs. 1.18 Ϯ 0.41). In six different rabbits without intravenous PBG, the neural arc transfer function did not change between two experimental runs with intervening interval of 10 min, excluding the possibility that the cumulative effects of anesthetics had altered the neural arc transfer function. In conclusion, excessive activation of the BJ reflex during acute myocardial ischemia may exert an adverse effect on AP regulation, not only by sympathetic suppression, but also by attenuating baroreflex dynamic gain. renal sympathetic nerve activity; transfer function; systems analysis; rabbits; carotid sinus baroreflex THE CIRCULATORY SYSTEM has several mechanoreceptors and chemoreceptors in a variety of regions. The cardiopulmonary region is rich in such receptors. The most vagal afferent fibers from the cardiopulmonary receptors to the vasomotor center are classified as C fibers.Activation of the cardiopulmonary chemosensitive vagal afferent fibers reduces arterial pressure (AP), heart rate (HR), and cardiac output (31). These responses, mediated by 5-hydroxytryptamine (5-HT 3 ) serotonergic receptors on the cardiopulmonary vagal afferent fibers, are known as the Bezold-Jarisch (BJ) reflex (2, 7, 32). Although its physiological importance remains debatable, the BJ reflex could play a significant role in developing pathological responses associated with acute myocardial ischemia (19,20,24). Elucidating the effects of the BJ reflex on the circulatory regulation would be useful for better understanding the pathophysiology of ischemic heart diseases (16, 27). The BJ reflex can be induced chemically with pharmacological agents such as 5-HT and ...

show abstract

Section: Clinical Implicationsupporting

confidence: 69%

Bezold-Jarisch reflex attenuates dynamic gain of baroreflex neural arc

Kashihara

Kawada²,

Yanagiya³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Methodological limitations associated with anesthesia and eserine administration have been described previously (10)(11)(12)(13). Other limitations to the present study are as follows.…”

Section: Discussionmentioning

confidence: 99%

“…We measured the concentration of ACh in the dialysate sample as an index of myocardial interstitial ACh level (10)(11)(12)(13). Materials and properties of the dialysis probe have been reported previously (2).…”

Section: Methodsmentioning

confidence: 99%

“…In protocol 2, the myocardial interstitial ACh response to local ouabain administration was examined (13,20). We collected a baseline dialysate sample while perfusing the dialysis probe with Ringer solution.…”

Section: Methodsmentioning

confidence: 99%

“…We have measured myocardial interstitial acetylcholine (ACh) levels by using a cardiac microdialysis technique in anesthetized cats (2,(10)(11)(12)(13). The ACh levels measured by the cardiac microdialysis were able to detect changes in the ACh kinetics in the vagal nerve terminals induced by pharmacological interventions, arterial baroreflex, or Bezold-Jarisch reflex (13). ACh levels increased during 60-min occlusion of the left anterior descending coronary artery (LAD) and decreased toward preocclusion level after LAD reperfusion (12).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Disruption of vagal efferent axon and nerve terminal function in the postischemic myocardium

Kawada¹,

Yamazaki

Akiyama

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

Despite the importance of vagal control over the ventricle, little is known regarding vagal efferent conduction and nerve terminal function in the postischemic myocardium. To elucidate postischemic changes in the cardiac vagal efferent neuronal function, we measured myocardial interstitial acetylcholine (ACh) levels by using in vivo cardiac microdialysis and examined the ACh responses to electrical stimulation of the vagi or local administration of ouabain in anesthetized cats. Sixty-minute occlusions of the left anterior descending coronary artery (LAD) followed by 60-min reperfusion abolished electrical stimulation-induced ACh release (20.4 Ϯ 3.9 vs. 0.9 Ϯ 0.4 nmol/l; means Ϯ SE, P Ͻ 0.01). In different groups of animals, 60-min LAD occlusion followed by 60-min reperfusion decreased but did not completely abolish ouabain-induced release of ACh (9.2 Ϯ 1.8 vs. 3.9 Ϯ 0.7 nmol/l; P Ͻ 0.05). These results indicate that function of the vagal efferent axon was completely interrupted, whereas the local ACh release was partially suppressed in the postischemic myocardium. The postischemic disruption of vagal efferent neuronal function might exert deleterious effects on cardiac regulation. cardiac microdialysis; vagal stimulation; ouabain; cats; acetylcholine AUTONOMIC DERANGEMENT ASSOCIATED with acute myocardial ischemia or infarction has deleterious effects on the heart (3, 6). The autonomic derangement occurs during postischemic as well as ischemic periods. Elucidating the underlying mechanisms of autonomic disturbance during the postischemic period is important to understand the pathophysiology of postischemic events such as those occurring after thrombolytic therapies. In the sympathetic nervous system, nerve terminal function as assessed by tyramine-induced norepinephrine release recovers 60-120 min after reperfusion of the coronary artery (1, 14). On the other hand, the myocardial response to electrical stimulation of sympathetic efferent neurons remains impaired up to 2 h after reperfusion, despite a preserved myocardial response to exogenous norepinephrine (5). Therefore, injury to sympathetic efferent axons (4, 8) is considered to be responsible for sympathetic denervation in the postischemic myocardium. However, conduction of the postganglionic axons in response to electrical stimulation of the epicardial sites was unaffected by regional ventricular ischemia (9), suggesting that the intrinsic cardiac fibers in the epicardial region were resistant to myocardial ischemia. We speculate that changes in the environment surrounding the postganglionic axons traveling through the midcardium affected the axonal conduction (15) even if the axon itself was not injured.In contrast to the sympathetic efferent nervous system, little is known regarding vagal efferent neuronal function in the postischemic myocardium in vivo. We have measured myocardial interstitial acetylcholine (ACh) levels by using a cardiac microdialysis technique in anesthetized cats (2, 10-13). The ACh levels measured by the cardiac microdialysis were ab...

show abstract

Chronic hypoxic incubation blunts a cardiovascular reflex loop in embryonic American alligator (Alligator mississippiensis)

2011

View full text Add to dashboard Cite

Hypoxia is a naturally occurring environmental challenge for embryonic non-avian reptiles, and this study is the first to investigate the impact of chronic hypoxia on a possible chemoreflex loop in a developing non-avian reptile. We measured heart rate and blood pressure in normoxic and hypoxic-incubated (10% O(2)) American alligator embryos (Alligator mississippiensis) at 70 and 90/95% of development. We hypothesized that hypoxic incubation would blunt embryonic alligators' response to a reflex loop stimulated by phenylbiguanide (PBG), a 5-HT(3) receptor agonist that stimulates vagal pulmonary C-fiber afferents. PBG injection caused a hypotensive bradycardia in 70 and 95% of development embryos (paired t tests, P < 0.05), a response similar to mammals breathing inspired air (all injections made through occlusive catheter in tertiary chorioallantoic membrane artery). Hypoxic incubation blunted the bradycardic response to PBG in embryos at 95% of development (two-way ANOVA, P < 0.01). We also demonstrated that the vagally mediated afferent limb of this reflex can be partially or completely blocked in ovo with a 5-HT(3) receptor blockade using ondansetron hydrochloride dihydrate (OHD), with a ganglionic blockade using hexamethonium, or with a cholinergic blockade using atropine. Atropine eliminated the hypotensive and bradycardic responses to PBG, and OHD and hexamethonium significantly blunted these responses. This cardiovascular reflex mediated by the vagus was affected by hypoxic incubation, suggesting that reptilian sympathetic and parasympathetic reflex loops have the potential for developmental plasticity in response to hypoxia. We suggest that the American alligator, with an extended length of time between each developmental stage relative to avian species, may provide an excellent model to test the cardiorespiratory effects of prolonged exposure to changes in atmospheric gases. This extended period allows for lengthy studies at each stage without the transition to a new stage, and the natural occurrence of hypoxia and hypercapnia in crocodilian nests makes this stress ecologically and evolutionarily relevant.

show abstract

In vivo assessment of acetylcholine-releasing function at cardiac vagal nerve terminals

Cited by 29 publications

References 29 publications

Bezold-Jarisch reflex attenuates dynamic gain of baroreflex neural arc

Bezold-Jarisch reflex attenuates dynamic gain of baroreflex neural arc

Disruption of vagal efferent axon and nerve terminal function in the postischemic myocardium

Chronic hypoxic incubation blunts a cardiovascular reflex loop in embryonic American alligator (Alligator mississippiensis)

Contact Info

Product

Resources

About