Reduced glutathione, dithiothreitol and cytochrome P-450 inhibitors do not influence hypoxic chemosensory responses in the rat carotid body.
Glomus cells and carotid sinus afferents are anatomically connected, and the chemical events in the glomus cells are expected to be conveyed reflexly as afferent signals. Accordingly, K(+) channel inhibition of the glomus cell membrane is expected to be followed by excitation of the afferents. In order to test the redox inhibition of K(+) channels of glomus cells by reduced glutathione (GSH), dithiothreitol (DTT) and by cytochrome P-450 inhibitors (clotrimazole and miconazole), we measured the carotid sinus nerve (CSN) discharge using an in vitro perfused adult rat carotid body (CB) in the presence and absence of these chemicals which are expected to excite the afferents. Our findings were that these agents did not stimulate the CSN activities during normoxia and kept the hypoxic responses intact. These results led us to conclude that the redox modulation of glomus cells was not conveyed to the afferents, and this functional disconnection did not support the redox hypothesis of O(2) chemoreception in the whole carotid body.
Roy
A
A
Department of Physiology, University of Pennsylvania School of Medicine, B-400 Richards Bldg., 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA.
Mokashi
A
A
Rozanov
C
C
Daudu
P A
PA
Lahiri
S
S
D000818:Animals; D002344:Carotid Body / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects; D002628:Chemoreceptor Cells / Q000187:drug effects*; D065607:Cytochrome P-450 Enzyme Inhibitors; D004229:Dithiothreitol / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D019163:Reducing Agents / Q000494:pharmacology; D013439:Sulfhydryl Reagents / Q000494:pharmacology*
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D015221:Potassium Channels; D019163:Reducing Agents; D013439:Sulfhydryl Reagents; D005978:Glutathione; D004229:Dithiothreitol