Cardio‐respiratory reflexes evoked by phenylbiguanide in rats involve vagal afferents which are not sensitive to capsaicin

Zhuang

et al. 2013

Neuroscience Letters

A previous study by the authors has shown that isoflurane (ISO), a commonly used volatile anesthetic, has an excitatory effect on bronchopulmonary C-fibers (PCFs). Since selective stimulation of PCFs by action on local 5-HT3 receptor could evoke an apnea, this current study addresses whether inhalation of ISO would facilitate the PCF 5-HT3 receptor-mediated apneic response and, if so, how. In anesthetized and spontaneously breathing rats, inhalation of 5% ISO markedly inhibited the apneic response to intra-atrium injection of phenylbiguanide (PBG, 25 µg/kg), a 5-HT3 receptor agonist, which was contrary to the hypothesis. Extracellular recording of the nodose ganglion neurons in anesthetized, paralyzed and ventilated rats revealed that ISO attenuated the PBG-elicited excitation of pulmonary C neurons. Furthermore, using the patch clamp technique, it was found that ISO depressed the PBG-induced inward current of the pulmonary C neurons labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) instilled previously into the lungs. These results suggest that ISO inhibits PCF 5-HT3 channel functions, and thereby attenuates PCF excitatory response to PBG, likely contributing to the diminution of the PBG-induced apnea by ISO in rats.

supporting

confidence: 66%

Isoflurane inhibits bronchopulmonary C-fiber-mediated apneic response to phenylbiguanide by depressing 5-HT3 receptor function in anesthetized rats

Zhuang

et al. 2013

Neuroscience Letters

“…As shown in Fig. 1, right atrial bolus injection of PBG induced RSB associated with bradycardia and hypotension, consistent with a previous report in rats (Dutta & Deshpande, 2010). The cardiorespiratory responses to PBG in this study were characterized by: 1) a shortened T E (−35%, from 0.40 ± 0.05 s to 0.26 ± 0.03 s, P < 0.01) with a latency of 1.88 ± 0.03 s; 2) a decreased MBP (−38%, from 88 ± 5 to 54 ± 6 mmHg, P < 0.01) and 3) a lowed HR (−40%, from 336 ± 23 to 201 ± 21 beats/min, P < 0.05).…”

Section: Resultssupporting

confidence: 92%

“…First, the production of RSB or an apnea is dependent on the stimulating intensity of PCFs. The RSB was induced by intra-atrial injection of a low dose of PBG while an apnea was also evoked if a high dose of PBG was used, and both types of responses disappeared after bilateral vagotomy (Coleridge & Coleridge, 1994; Moreira et al , 2007; Dutta & Deshpande, 2010). Second, μ-receptor agonists can excite unmyelinated C type neurons in the nodose ganglion of rabbits (Higashi et al , 1982; Crain & Shen, 1990) in vitro and stimulate PCFs to induce an apnea in vivo (Willette & Sapru, 1982).…”

Section: Discussionmentioning

confidence: 99%

“…PBG (0.05 ml) was first slowly loaded into the catheter with a volume of 0.08 ml and then quickly flushed into the right atrium with 0.12 ml saline, which was the same for the following studies. A previous study has shown that 3 μg/kg of PBG leads to a maximal tachypnea (Dutta & Deshpande, 2010). Therefore, this dose was chosen as the initial dose to evoke the RSB in this study.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Activation of opioid μ-receptors, but not δ- or κ-receptors, switches pulmonary C-fiber-mediated rapid shallow breathing into an apnea in anesthetized rats

Respiratory Physiology & Neurobiology

Zhou

et al. 2012

Rapid shallow breathing (RSB) is mainly mediated by bronchopulmonary C-fibers (PCFs). We asked whether this RSB could be modulated by opioid. In anesthetized rats right atrial bolus injection of phenylbiguanide (PBG) to evoke RSB was repeated after: 1) intravenously giving fentanyl (μ-receptor agonist), DPDPE (δ-receptor agonist), or U-50488H (κ-receptor agonist); 2) fentanyl (iv) following naloxone methiodide, a peripheral opioid receptor antagonist; 3) bilateral microinjection of fentanyl into the nodose ganglia; 4) fentanyl (iv) with pre-blocking histamine H1 and H2 receptors by diphenhydramine and ranitidine. Systemic fentanyl challenge, but not DPDPE or U-50488H, switched the PBG-induced RSB to a long lasting apnea. This switch was blocked by naloxone methiodide rather than diphenhydramine and ranitidine. After microinjecting fentanyl into the nodose ganglia, PBG also produced an apnea. Our results suggest that activating μ-receptors is capable of turning the PCF-mediated RSB into an apnea, at least partly, via facilitating PCFs’ activity and this switching effect appears independent of the released histamine.

“…PCFs are critical in modulating respiratory frequency, and its excitatory or inhibitory impacts on respiratory frequency are dependent on the stimulating intensity on these sensory nerve endings. For example, to stimulate PCF, right atrial bolus injection of phenylbiguanide (PBG) at a low dose evokes RSB, but it at a high dose induces an apnea (Coleridge and Coleridge, 1994; Dutta and Deshpande, 2010; Moreira et al, 2007). Because μ-receptor agonists could sensitize/activate PCFs (Willette and Sapru, 1982), we previously tested whether systemic administration of μ-receptor agonist fentanyl would switch the PCFs-mediated RSB into an apnea via sensitizing PCFs (Zhang et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Contribution of central μ-receptors to switching pulmonary C-fibers-mediated rapid shallow breathing into an apnea by fentanyl in anesthetized rats

Zhang¹,

Zhang²,

Zhuang³

et al. 2012

Brain Research

Our previous study has shown that activating peripheral μ-receptors is necessary for switching the bronchopulmonary C-fibers (PCFs)-mediated rapid shallow breathing (RSB) into an apnea by systemic administration of fentanyl. The brainstem nuclei, such as the medial nucleus tractus solitarius (mNTS) and the Pre-Botzinger Complex (PBC), are required for completing the PCF-mediated respiratory reflexes. Moreover, these areas contain abundant μ-receptors and their activation prolongs expiratory duration (TE). Thus, we asked if central μ-receptors, especially those in the mNTS and PBC, are involved in fully expressing this RSB-apnea switch by fentanyl. In anesthetized rats, the cardiorespiratory responses to right atrial injection of phenylbiguanide (PBG, 3–6 μg/kg) were repeated after: 1) fentanyl (iv), a μ-receptor agonist, alone (8 μg/kg, iv); 2) fentanyl following microinjection of naloxone methiodide (NXM, an opioid receptor antagonist) into the cisterna magna (10 μg/4 μl); 3) the bilateral mNTS (10 mM, 20 nl); or 4) PBC (10 mM, 20 nl). Our results showed that PBG shortened TE by 37 ± 6 % (RSB, from 0.41 ± 0.05 to 0.26 ± 0.03 s, P < 0.01), but it markedly prolonged TE by 5.8-fold (an apnea, from 0.50 ± 0.04 s to 2.9 ± 0.57 s, P < 0.01) after fentanyl (iv). Pretreatment with NXM injected into the cisterna magna or the PBC, but not the mNTS, prevented the fentanyl-induced switch. This study, along with our previous results mentioned above, suggests that although peripheral μ-receptors are essential for triggering the fentanyl-induced switch, central μ-receptors, especially those in the PBC, are required to fully exhibit such switch.