Abstract

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 (fx). 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 (PO2?125 Torr, pH 7.40 at 38°C). Hypoxia (PO2?30 Torr), NaCN and nicotine (1-100 ?g) and S-nitroso-N-acetylpenicillamide (SNAP, 300-600 ?g) increased fx. Oligomycin (12.5-25 ?g), antimycin A (10 ?g) and FCCP (5 ?M) transiently increased fx. 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. Copyright © 2002 .