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

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 GABAA 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.

Electrophysiological-anatomic correlates of ATP-triggered vagal reflex in the dog. V. Role of purinergic receptors

The mechanism of extracellular ATP-triggered vagal depressor reflex was further studied in a closed-chest canine model. Adenosine and ATP were administered individually in equimolar doses (0.01–1.0 μmol/kg) into the right coronary artery (RCA) and left circumflex coronary artery (LCA). When administered into the RCA, adenosine and ATP exerted an identical and relatively small negative chronotropic effect on sinus node automaticity; the time to peak negative chronotropic effect was ≥7 s. When administered into the LCA, adenosine had no effect on sinus node automaticity, whereas ATP markedly suppressed sinus node automaticity. This effect of ATP 1) reached its peak in <2 s after its administration, 2) was short lasting, and 3) was completely abolished by either intravenous administration of the muscarinic cholinergic blocker atropine (0.2 mg/kg) or intra-LCA administration of 2′,3′- O-(2,4,6 -trinitrophenyl)-ATP (TNP-ATP), a potent P2X2/3 purinergic receptor (P2X2/3R) antagonist, but not by diinosine pentaphosphate (Ip5I), a potent inhibitor of P2X1R and P2X3R. Repetitive administrations of ATP were not associated with reduced effects, indicative of receptor desensitization, thereby excluding the involvement of the rapidly desensitized P2X1R in the action of ATP. It was concluded that ATP triggers a cardio-cardiac vagal depressor reflex by activating P2X2/3R located on vagal sensory nerve terminals localized in the left ventricle. Because these terminals mediate vasovagal syncope, these data could suggest a mechanistic role of extracellular ATP in this syndrome and, in addition, give further support to the hypothesis that endogenous ATP released from ischemic myocytes is a mediator of atropine-sensitive bradyarrhythmias associated with left ventricular myocardial infarction.

Chemical stimulation of cardiac receptors attenuates locomotion in mesencephalic cats

Pickar, Joel G. Chemical stimulation of cardiac receptors attenuates locomotion in mesencephalic cats. J. Appl. Physiol. 83(1): 113–119, 1997.—The purpose of the present investigation was to determine whether chemical stimulation of cardiac receptors is sufficient to inhibit locomotion. Decerebrate, unanesthetized cats were induced to walk on a treadmill by electrically stimulating the mesencephalic locomotor region (MLR). Cardiac receptors were stimulated by injecting nicotine (62.3 ± 8.6 μg/kg, mean ± SE) into the pericardial sac. Cardiac nerve activity was reversibly blocked by injecting procaine (2%) into the pericardial sac. Locomotion was monitored by using bipolar needle electrodes inserted into the lateral gastrocnemius (LG) and tibialis anterior (TA) muscles. Integrated electromyographic (iEMG) activity from each muscle was quantified on a step-by-step basis. Intrapericardial (ipc) nicotine inhibited locomotion and evoked the coronary chemoreflex. Blood pressure and heart rate decreased significantly by 45.6 ± 7.1 mmHg and 59.3 ± 12.3 beats/min, respectively. Nicotine ipc significantly reduced iEMG activity by 24–28% in the LG muscles. The TA muscles were not affected consistently by ipc nicotine. The locomotor inhibition and the depressor reflex paralleled each other and occurred within 5 s of nicotine injection. Procaine ipc blocked the nicotine-induced locomotor inhibition and depressor reflex. The effects of procaine were largely reversible, because ipc nicotine reduced iEMG activity in the LG (25–46%) but not in the TA muscles after washing procaine from the pericardial sac. These results demonstrate that cardiac receptors sensitive to nicotine inhibit MLR-induced locomotion in the decerebrate cat. These findings indicate the presence of a neural pathway from the heart whereby endogenous stimuli could reflexly alter motor control.

Coronary chemoreflex evoked by intrapericardial nicotine has a somatic component

Stimulation of vagally innervated cardiac or pulmonary receptors reflexly evokes depressor responses called the coronary chemoreflex and pulmonary depressor reflex, respectively. The efferent arm of the pulmonary depressor reflex contains a somatic component wherein monosynaptic and polysynaptic muscle reflexes are attenuated. The purpose of the present investigation was to determine whether the efferent arm of the coronary chemoreflex also attenuates the monosynaptic knee-jerk reflex. Cardiac receptors were stimulated by injection of nicotine and bradykinin into the pericardial sac of 15 chloralose-anesthetized (50 mg/kg) cats. The knee-jerk reflex was elicited by tapping the patellar tendon intermittently. Intrapericardial nicotine attenuated the knee-jerk reflex by -26.2 +/- 6.5%. The attenuation was mediated by the vagus nerves, because vagotomy abolished the nicotine-induced attenuation. Stimulation of cardiac receptors evoked the attenuation, because blockade using intrapericardial procaine abolished the nicotine-induced attenuation. On the other hand, intrapericardial bradykinin augmented the knee-jerk reflex by 17.5 +/- 3.3%. The effect was not mediated by the vagus nerves; vagotomy did not abolish the bradykinin-induced augmentation. Changes in the knee-jerk reflex were not correlated with changes in blood pressure or heart rate evoked by intrapericardial nicotine or bradykinin. These findings demonstrate that reflex somatomotor responses accompany the reflex autonomic responses elicited by cardiac receptors. The somatic component of the vagally mediated coronary chemoreflex could contribute to the fainting reaction associated with exertional syncope of aortic stenosis and vasovagal syncope.

Electrophysiological-anatomic correlates of ATP-triggered vagal reflex in dogs. II. Vagal afferent traffic

Extracellular ATP can act on chemosensitive vagal C-fiber nerve terminals in the lungs, thereby eliciting a pulmonary-cardiac depressor reflex. Previous studies have shown a right vagal dominance in afferent traffic elicited by intra-right atrial ATP. To elucidate the mechanism of this phenomenon, the following hypotheses were tested in a canine model. 1) Intra-right and intra-left pulmonary ATP elicit neural afferent traffic, which travels via the right and left vagus nerves, respectively. 2) Intra-right vs. intra-left pulmonary ATP causes similar suppression of sinus node automaticity. Data obtained in this study support both hypotheses and suggest that right vagal dominance in afferent neural traffic elicited by ATP is probably due to the action of ATP and/or its metabolites on nonpulmonary tissues.