title: Cellular mechanisms of hypoxia-induced contraction in human and rat pulmonary arteries.
abstract: The effect of hypoxia was investigated in human (HPA) and rat (RPA) pulmonary arteries. Hypoxia-induced contraction was 95 +/- 8.7% and 9.3 +/- 4.8% of the control response to K(+)-rich (80 mM) solution in HPA and RPA, respectively (n = 10). When RPA strips were precontracted with phorbol 12,13 dibutyrate (0.2 microM), hypoxia elicited a larger contraction (105 +/- 13.4% of the control response, n = 8). In both types of artery, hypoxia-induced contraction was dependent on the extracellular calcium concentration (66 +/- 8.4% and 40 +/- 14.4%, reduction for 1.25 mM Ca2+ in HPA and RPA, respectively, n = 6) and was inhibited by verapamil (0.05-10 microM) and nifedipine (0.05-1 microM). Glibenclamide (5-10 microM) increased the amplitude of hypoxia-induced contraction (+42 +/- 5.3%, n = 5). Hypoxia-induced contraction was blocked by cromakalim (1 microM) and this effect was reversed by glibenclamide (5 microM). This contraction was also inhibited by iodoacetic acid (250 microM). In beta-escin skinned pulmonary arterial strips, hypoxia had no effect on the calcium concentration-tension relationship. These results suggest that the O2 sensor in the pulmonary artery is located on the vascular smooth muscle plasmalemma. Hypoxia-induced contraction is dependent on calcium influx through voltage sensitive calcium channels. Its amplitude is modulated by the functioning of potassium channels.
authors.affiliation: Laboratoire de Physiologie, Université de Bordeaux II, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Savineau
authors.forename: P
authors.initials: P
authors.lastname: Gonzalez de la Fuente
authors.forename: R
authors.initials: R
authors.lastname: Marthan
mesh_terms: D000368:Aged; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D019806:Cromakalim; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D066298:In Vitro Techniques; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D009543:Nifedipine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D001578:Benzopyrans; D015220:Calcium Channels; D007461:Iodoacetates; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D014700:Verapamil; D009543:Nifedipine; D005905:Glyburide; D002118:Calcium; D019807:Iodoacetic Acid