title: Endothelin, but not angiotensin II, contributes to the hypoxic contractile response of large isolated pulmonary arteries in the rat.
abstract: The aims of this study were to investigate whether angiotensin II and/or endothelin could contribute to the hypoxic contractile response of isolated rat pulmonary artery. Experiments were performed for 1 h on noradrenaline precontracted arterial rings in hypoxic conditions (95% N2 and 5% CO2). Nicardipine, lisinopril, losartan, phosphoramidon, FR139317 and bosentan were used to block Ca2+ channels, angiotensin I-converting enzyme, AT1 receptors, endothelin-converting enzyme, ETA receptors, and ETA/ETB receptors, respectively. The profile of the hypoxic contractile response was biphasic, displaying, after a short relaxation, a weak and transient contraction (from 2-4 min) and then, before complete relaxation, a slowly developed but sustained contraction (from 14-60 min). Endothelium removal abolished the transient contraction and reduced (-59%) the sustained contraction. Nicardipine did not modify the transient contraction, but concentration-dependently decreased (from -35% to -100%) the sustained contraction (P = 0.024). Lisinopril and losartan did not affect the response (P = 0.418 and P = 0.973, respectively). Bosentan did not modify the transient contraction, but concentration-dependently decreased (from -14% to -71%) the sustained contraction (P = 0.016), whereas phosphoramidon and FR139317 did not affect the response (P = 0.830 and P = 0.806, respectively).
  
  
  CONCLUSIONS
  In rat, (i) both phases of the hypoxic contractile response are endothelium-dependent and independent of angiotensin II; (ii) the transient contraction does not depend on endothelin; (iii) the sustained contraction, which involves calcium influx, appears partly dependent on mature endothelin released from storage granules by stimulating ETB receptors.
authors.affiliation: Laboratoire de Pharmacologie Expérimentale et Clinique, UPRES EA 1263 Electrophysiologie et Hémodynamique de l'Insuffisance Cardiaque Faculté de Médecine, Rennès, France.
authors.forename: D
authors.initials: D
authors.lastname: Pape
authors.forename: S
authors.initials: S
authors.lastname: Goineau
authors.forename: P
authors.initials: P
authors.lastname: Guillo
authors.forename: X
authors.initials: X
authors.lastname: Durand-Castel
authors.forename: E
authors.initials: E
authors.lastname: Bellissant
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D000077300:Bosentan; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005110:Extracellular Space / Q000378:metabolism; D006020:Glycopeptides / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D017706:Lisinopril / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009529:Nicardipine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001381:Azepines; D002121:Calcium Channel Blockers; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D006020:Glycopeptides; D007211:Indoles; D013449:Sulfonamides; D000804:Angiotensin II; C079574:FR 139317; D000803:Angiotensin I; D009529:Nicardipine; D017706:Lisinopril; D019808:Losartan; D000077300:Bosentan; D002118:Calcium; C008890:phosphoramidon