title: Adenosine and ATP cause nitric oxide-dependent pulmonary vasodilation in fetal lambs.
abstract: We investigated the hypothesis that the purine nucleotide ATP and its nucleoside adenosine cause pulmonary vasodilation in fetal lambs by the release of nitric oxide (NO). We also investigated the potential role of K(+)(ATP) channels in mediating the effects of ATP and adenosine on NO. We surgically prepared 28 fetal lambs to measure pulmonary and systemic pressures and pulmonary flow. We investigated the effects of glibenclamide and pinacidil (inhibitor and agonist, respectively, for K(+)(ATP) channels), N-nitro-L-arginine (N-LA) and its methyl ester, N-nitro-L-arginine methyl ester (L-NAME) (inhibitors of endothelium-derived NO synthesis), and U46619 (a thromboxane mimetic) on pulmonary vasodilation caused by adenosine and ATP. Adenosine decreased the pulmonary artery pressure and pulmonary vascular resistance (PVR) at doses of 0.08-2.5 microM/kg/min and increased the left pulmonary flow at doses of 0.3-2.5 microM/kg/min in control experiments. N-LA, L-NAME and glibenclamide attenuated the effects of adenosine at doses of < 2.5 microM/ kg/min and pinacidil potentiated its effects. ATP decreased the pulmonary artery pressure and PVR and increased the pulmonary flow at doses of 0.15-2.5 microM/kg/min in control experiments. N-LA and L-NAME attenuated the effects of ATP at doses of < 2.5 microM/kg/min, whereas glibenclamide and pinacidil had no effect on the response to ATP. U46619 increased the basal pulmonary vascular tone, but did not significantly alter the vasodilative responses to ATP and adenosine. In conclusion, adenosine and ATP cause NO-dependent pulmonary vasodilation in fetal lambs. The activation of K(+)(ATP) channels plays a role in adenosine-induced pulmonary vasodilation. The mechanism by which ATP causes NO release and pulmonary vasodilation requires further investigation.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA. gkonduri@pol.net
authors.forename: G G
authors.initials: GG
authors.lastname: Konduri
authors.forename: S
authors.initials: S
authors.lastname: Mital
mesh_terms: D000241:Adenosine / Q000494:pharmacology / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D005333:Fetus / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D012756:Sheep / Q000196:embryology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D015221:Potassium Channels; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D000241:Adenosine