Muscarinic M1 receptors mediate the increase in pulmonary resistance during vagus nerve stimulation in dogs.
The physiologic roles of the 2 muscarinic receptors (M1 and M2) in the vagal control of pulmonary resistance were studied by comparing the effects of pirenzepine (PZ, M1-blocker), gallamine (GAL, M2-blocker), and atropine (AT, M1- and M2-blocker) on the increase in pulmonary resistance (RL) and on the reduction in heart rate (HR) during bilateral cervical vagus nerve stimulation in 18 anesthetized (chloralose and urethane) and paralyzed (vecuronium) dogs. PZ, AT, and GAL all inhibited the reduction in HR during vagus nerve stimulation, although the inhibition required relatively high doses of PZ and GAL. AT and PZ inhibited the increase in RL during vagus nerve stimulation. The ratio of the dose needed to inhibit by 50% the HR response to the dose needed to inhibit by 50% the RL response was approximately 45:1 for PZ, 12:1 for AT, and less than 0.4:1 for GAL. Thus, compared with AT, PZ is a more selective blocker of vagally induced increases in RL, indicating that M1 receptors are present in the airway smooth muscle of intact anesthetized dogs. In the same dose range as that which caused the inhibition of the HR response, GAL had no consistent effect on the increase in RL during vagus nerve stimulation, indicating that M2 receptors do not mediate the increase in RL in intact anesthetized dogs.
Beck
K C
KC
Division of Anesthesia Research, Mayo Clinic, Rochester, Minnesota.
Vettermann
J
J
Flavahan
N A
NA
Rehder
K
K
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D005703:Gallamine Triethiodide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000294:innervation*; D008297:Male; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology*
D011976:Receptors, Muscarinic; D010890:Pirenzepine; D001285:Atropine; D005703:Gallamine Triethiodide