Fentanyl Turns Pulmonary C‐Fiber ‐Mediated Rapid Shallow Breathing into an Apnea in Anesthetized Rats

Abstract

It is generally accepted that rapid shallow breathing (RSB) is primarily mediated by pulmonary C‐fibers (PCFs). A low dose of PCF stimulants induces RSB while a high dose produces an apnea, suggesting that the occurrence of RSB or an apnea depends on the excitatory degree of the PCFs. Because vagal nerves contain opioid receptors and PCF activity is increased by opioids, we asked if opioids would sensitize PCFs to turn the PCF‐mediated RSB into an apnea. Right atrial injection of the selective PCF stimulant phenylbiguanide (PBG) was given before and after intravenous administration of selective μ‐, δ‐, or κ‐receptor agonists (fentanyl, 6 μg/kg; DPDPE, 2 mg/kg; or U‐50488H, 4 mg/kg, respectively) in anesthetized and spontaneously breathing rats. PBG at a low dose (3–5 μg/kg) shortened the expiratory duration (TE) from 0.40 ± 0.04 s to 0.27 ± 0.05 s (P < 0.01), while it produced a long‐lasting apnea (0.52 ± 0.06 vs. 3.40 ± 0.46 s for TE, P < 0.01) after fentanyl. PBG at a high dose (10 μg/kg) also induced an apnea (2.3 ± 0.8 s) that was remarkably prolonged by fentanyl (9.1 ± 1.5 s). These facilitating effects of fentanyl were eliminated by naloxone (5 mg/kg, iv, an opioid receptor antagonist). DPDPE or U‐50488H failed to turn the PBG‐induced RSB into an apnea. This study suggests that opioids can facilitate the PCF‐mediated respiratory response through μ‐ rather than δ‐ or κ‐receptors. (Supported by ALA RT‐83131‐N)