title: Modification by CO2 of endothelin-1-induced contraction of isolated guinea pig trachea.
abstract: To investigate the effect of changes in CO2 tension on airway smooth muscle tone induced by various agonists, contractile responses to acetylcholine, histamine and endothelin-1 (ET-1) were studied in isolated guinea pig tracheae at very low PCO2 (16 +/- 0 mmHg, n = 38), moderately low PCO2 (28 +/- 0 mmHg, n = 23), normal PCO2 (38 +/- 1 mmHg, n = 70) or high PCO2 (94 +/- 1 mmHg, n = 32). The minimum concentration of ET-1 (10(-10) M) needed to induce contractions was lower than that of acetylcholine (10(-7) M) and histamine (10(-7) M) at normal PCO2. Changes in PCO2 did not significantly affect acetylcholine- or histamine-induced contractions. In contrast, very low and moderately low PCO2 attenuated the contractions induced by ET-1, but high PCO2 potentiated those induced by a high concentration of ET-1. Very low PCO2 with normal pH and with high pH attenuated the contractions caused by ET-1, whereas normal PCO2 with high pH did not. These results suggest that ET-1-induced airway smooth muscle contraction can be modified by PCO2 per se. Aspirin and indomethacin potentiated the responses to ET-1 at very low PCO2 more than at normal PCO2, but attenuated the responses to low concentration of ET-1 at high PCO2. These results also suggest that cyclooxygenase-related eicosanoids are involved in the effects of PCO2 on ET-1-induced contractions.
authors.affiliation: Department of Anesthesiology, Niigata University School of Medicine, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tsukui
authors.forename: S
authors.initials: S
authors.lastname: Fukuda
authors.forename: T
authors.initials: T
authors.lastname: Honda
authors.forename: H
authors.initials: H
authors.lastname: Fujihara
authors.forename: K
authors.initials: K
authors.lastname: Sakuma
authors.forename: K
authors.initials: K
authors.lastname: Shimoji
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D016232:Endothelins / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
chemical_list: D016232:Endothelins; D002245:Carbon Dioxide; D011189:Potassium Chloride; D006632:Histamine; D000109:Acetylcholine; D001241:Aspirin; D007213:Indomethacin