Carotid body chemosensory excitation induced by nitric oxide: involvement of oxidative metabolism.
Nitric oxide (NO) produces a dual effect on carotid body (CB) oxygen chemoreception. At low concentration, NO inhibits chemosensory response to hypoxia, while in normoxia, medium and high [NO] increases the frequency of carotid chemosensory discharges (f(x)). Since NO and peroxynitrite inhibit mitochondrial respiration, it is plausible that the NO-induced excitation may depend on the mitochondrial oxidative metabolism. To test this hypothesis, we studied the effects of oligomycin, FCCP and antimycin A that produce selective blockade of hypoxic and NaCN-induced chemosensory responses, leaving nicotinic response less affected. CBs excised from pentobarbitone-anaesthetised cats were perfused in vitro with Tyrode (P(O(2)) approximately 125 Torr, pH 7.40 at 38 degrees C). Hypoxia (P(O(2)) approximately equal 30 Torr), NaCN and nicotine (1-100 microg) and S-nitroso-N-acetylpenicillamide (SNAP, 300-600 microg) increased f(x). Oligomycin (12.5-25 microg), antimycin A (10 microg) and FCCP (5 microM) transiently increased f(x). Subsequently, chemosensory responses to hypoxia, NaCN and SNAP were reduced or abolished, while the response to nicotine was less affected. The electron donor system tetramethyl-p-phenylene diamide and ascorbate that bypasses the electron chain blockade produced by antimycin A, restores the excitatory responses to NaCN and SNAP. Present results suggest that the chemoexcitatory effect of NO depends on the integrity of mitochondrial metabolism.
Laboratorio de Neurobiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Casilla 1, 114-D, Santiago, Chile.
Matias
M
Mosqueira
Rodrigo
R
Iturriaga
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000968:Antimycin A / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002344:Carotid Body / Q000187:drug effects / Q000378:metabolism*; D002415:Cats; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology; D007202:Indicators and Reagents; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011042:Poisons / Q000494:pharmacology; D012119:Respiration; D012966:Sodium Cyanide / Q000494:pharmacology; D013772:Tetramethylphenylenediamine; D014475:Uncoupling Agents / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D009840:Oligomycins; D011042:Poisons; D014475:Uncoupling Agents; D009569:Nitric Oxide; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D000968:Antimycin A; D012966:Sodium Cyanide; D013772:Tetramethylphenylenediamine; D001205:Ascorbic Acid