Stimulus interaction between CO2 and almitrine in the cat carotid chemoreceptors.
The hypothesis that augmentation of the carotid chemoreceptor response to hypoxia by almitrine is due in part to an increased response to CO2 was tested by using single or few fiber preparation of carotid body chemosensory fibers in 12 cats anesthetized with alpha-chloralose. To differentiate between the plausible mechanisms of effects, we also tested the responsiveness of the afferents to cyanide and nicotine before and after almitrine. After a saturation dose of almitrine (1 mg.kg-1 followed by 0.5 mg.kg-1.h-1) the chemosensory responses to CO2 strikingly increased even during hyperoxia: the afferents showing an increased transient peak activity at the onset of hypercapnia, an augmented steady-state response to CO2 stimulus, and a decreased arterial PCO2 stimulus threshold. Thus, the effect of almitrine on carotid chemoreceptor response to hypoxia could be explained, at least in part, by its multiplicative stimulus interaction with CO2. After almitrine, the chemoreceptor response to cyanide, which is dependent on arterial PO2, was not particularly augmented relative to those of nicotine. Accordingly, the O2-sensing mechanism does not appear to be the primary site of almitrine effect. The results also indicate that the site of CO2 chemoreception resides downstream from those of hypoxia.
Lahiri
S
S
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia 19104-6085.
Mokashi
A
A
Huang
W
W
Sherpa
A K
AK
Di Giulio
C
C
D015765:Almitrine; D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology*; D002344:Carotid Body / Q000187:drug effects*; D002415:Cats; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003486:Cyanides / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D000860:Hypoxia / Q000503:physiopathology; D009538:Nicotine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*
D000697:Central Nervous System Stimulants; D003486:Cyanides; D010879:Piperazines; D002245:Carbon Dioxide; D009538:Nicotine; D015765:Almitrine