Inhibitory effects of NO on carotid body: contribution of neural and endothelial nitric oxide synthase isoforms.
We tested the hypothesis that nitric oxide (NO) produced within the carotid body is a tonic inhibitor of chemoreception and determined the contribution of neuronal and endothelial nitric oxide synthase (eNOS) isoforms to the inhibitory NO effect. Accordingly, we studied the effect of NO generated from S-nitroso-N-acetylpenicillamide (SNAP) and compared the effects of the nonselective inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME) and the selective nNOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole (TRIM) on chemosensory dose-response curves induced by nicotine and NaCN and responses to hypoxia (Po(2) approximately 30 Torr). CBs excised from pentobarbitone-anesthetized cats were perfused in vitro with Tyrode at 38 degrees C and pH 7.40, and chemosensory discharges were recorded from the carotid sinus nerve. SNAP (100 microM) reduced the responses to nicotine and NaCN. l-NAME (1 mM) enhanced the responses to nicotine and NaCN by increasing their duration, but TRIM (100 microM) only enhanced the responses to high doses of NaCN. The amplitude of the response to hypoxia was enhanced by l-NAME but not by TRIM. Our results suggest that both isoforms contribute to the NO action, but eNOS being the main source for NO in the cat CB and exerting a tonic effect upon chemoreceptor activity.
Valdés
Viviana
V
Laboratorio de Neurobiologia, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Casilla 114-D, Santiago 1, Chile.
Mosqueira
Matías
M
Rey
Sergio
S
Del Rio
Rodrigo
R
Iturriaga
Rodrigo
R
D000818:Animals; D002344:Carotid Body / Q000502:physiology*; D002415:Cats; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D012966:Sodium Cyanide / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007093:Imidazoles; D020030:Nitric Oxide Donors; C098186:1-(2-trifluoromethylphenyl)imidazole; D009569:Nitric Oxide; D009538:Nicotine; D026423:S-Nitroso-N-Acetylpenicillamine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D012966:Sodium Cyanide; D019331:NG-Nitroarginine Methyl Ester