Modulation of cardiopulmonary depressor reflex in nucleus ambiguus by electroacupuncture: roles of opioids and γ-aminobutyric acid

Abstract

Stimulation of cardiopulmonary receptors with phenylbiguanide (PBG) elicits depressor cardiovascular reflex responses, including decreases in blood pressure and heart rate mediated in part by the brain stem parasympathetic cardiac neurons in the nucleus ambiguus (NAmb). The present study examined NAmb neurotransmitter mechanisms underlying the influence of electroacupuncture (EA) on the PBG-induced hypotension and bradycardia. We hypothesized that somatic stimulation during EA modulates PBG responses through opioid and γ-aminobutyric acid (GABA) modulation in the NAmb. Anesthetized and ventilated cats were studied during repeated stimulation with PBG or cardiac vagal afferents while low-frequency EA (2 Hz) was applied at P5-6 acupoints overlying the median nerve for 30 min and NAmb neuronal activity, heart rate, and blood pressure were recorded. Microinjection of kainic acid into the NAmb attenuated the PBG-induced bradycardia from -60 ± 11 to -36 ± 11 beats/min. Likewise, EA reduced the PBG-induced depressor and bradycardia reflex by 52 and 61%, respectively. Cardiac vagal afferent evoked preganglionic cellular activity in the NAmb was reduced by EA for about 60 min. Blockade of opioid or GABA(A) receptors using naloxone and gabazine reversed the EA-related modulation of the evoked cardiac vagal activity by 73 and 53%, respectively. Similarly, naloxone and gabazine reversed EA modulation of the negative chronotropic responses from -11 ± 5 to -23 ± 6 and -13 ± 4 to -24 ± 3 beats/min, respectively. Thus EA at P5-6 decreases PBG evoked hypotension and bradycardia as well as the NAmb PBG-sensitive preganglionic cardiac vagal outflow through opioid and GABA neurotransmitter systems.

Medullary GABAergic mechanisms contribute to electroacupuncture modulation of cardiovascular depressor responses during gastric distention in rats

“…Gabazine microinjection into the NAmb briefly decreased heart rate by an average of 10 beats per minute (bpm). These changes are similar to those observed by us and others investigating neurotransmitter action in these nuclei (15,25,41).…”

“…EA at P5-P6 acupoints activates NAmb neurons in close proximity to enkephalinergic processes, implying that EA exerts at least part of its cardiovascular actions through this nucleus and that enkephalin participates in EA processing in this region (13). Furthermore, we observed that EA at the P5-P6 acupoints inhibited evoked neuronal discharge in the NAmb during vagal afferent fiber stimulation (41), an action that was attenuated by blockade of GABA A receptors with gabazine. GABA A receptor blockade in this region also reverses EA-related modulation of bradycardia responses elicited during stimulation of cardiopulmonary vagal afferent endings in cats by intravenous administration of PBG, a 5-HT 3 receptor agonist (41).…”

“…Gallamine triethiodide (4 mg/kg) was administered intravenously before application of 30 min EA (2-4 Hz, 1-4 mA, 0.5 ms) to avoid muscle movement during stimulation of median nerves. Of note, motor nerve stimulation does not participate in the EA-cardiovascular response, since we have shown EA inhibition of reflex cardiovascular responses following muscle paralysis (22,41). Application of EA lasted 30 min, while gastric distention during somatic stimulation occurred every 10 min.…”

“…The NAmb is well recognized as an important site for regulation of parasympathetic outflow through its action on preganglionic cardiac vagal efferent fibers (41). In this regard, we recently have shown that this region participates in gastric distention-induced bradycardia associated with hypercapnia and respiratory acidosis (39).…”

“…We have observed that the bradycardia responses to intravenous phenylbiguanide, which activates cardiopulmonary afferents to reflexly lower heart rate, is reduced by low-frequency low-current EA at P5-P6 through a GABA A mechanism involving vagal preganglionic nucleus ambiguus (NAmb) neurons (41). More recently, we have shown that distending the stomach decreases heart rate in hypercapnic-acidotic rats through both sympathoinhibition and vagal excitation (39).…”