Doxapram stimulates the carotid body via a different mechanism than hypoxic chemotransduction.
To determine if doxapram stimulates the carotid body through the same mechanism as hypoxia, we compared the effects of doxapram and hypoxia on isolated-perfused carotid bodies in rabbits. Doxapram stimulated the carotid body in a dose-dependent manner. In Ca(2+)-free solution, neither doxapram nor hypoxia stimulated the carotid body. Although, doxapram had an additive effect on the carotid body chemosensory response to hypercapnia, a synergistic effect was not observed. Also, we investigated the various K(+) channel activators on the response to doxapram and hypoxia: pinacidil and levcromakalim as ATP-sensitive K(+) channel activators; NS-1619 as a Ca(2+)-sensitive K(+) channel activator; and halothane as a TASK-like background K(+) channel activator. The hypoxic response was partially reduced by halothane only, while pinacidil, levcromakalim and NS-1619 had no effect. Interestingly, the effect of doxapram was partially inhibited by NS-1619. Neither pinacidil nor levcromakalim affected the stimulatory effect of doxapram. We conclude that doxapram stimulates the carotid body via a different mechanism than hypoxic chemotransduction.
Takahashi
Toru
T
First Department of Medicine, Asahikawa Medical College, 2-1-1-1 Midorigaoka Higash, Asahikawa 078-8510, Japan. sas@asahikawa-med.ac.jp
Osanai
Shinobu
S
Nakano
Hitoshi
H
Ohsaki
Yoshinobu
Y
Kikuchi
Kenjiro
K
D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002344:Carotid Body / Q000187:drug effects*; D002346:Carotid Sinus / Q000187:drug effects / Q000294:innervation; D019806:Cromakalim / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004315:Doxapram / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D019141:Respiratory System Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D001562:Benzimidazoles; D015221:Potassium Channels; D019141:Respiratory System Agents; D014665:Vasodilator Agents; D019806:Cromakalim; C086491:NS 1619; D020110:Pinacidil; D004315:Doxapram; D006221:Halothane