title: Extracellular ATP signaling in the rabbit lung: erythrocytes as determinants of vascular resistance.
abstract: Previously, it was reported that red blood cells (RBCs) are required to demonstrate participation of nitric oxide (NO) in the regulation of rabbit pulmonary vascular resistance (PVR). RBCs do not synthesize NO; hence, we postulated that ATP, present in millimolar amounts in RBCs, was the mediator, which evoked NO synthesis in the vascular endothelium. First, we found that deformation of RBCs, as occurs on passage across the pulmonary circulation with increasing flow rate, evoked increments in ATP release. Here, ATP (300 nM), administered to isolated, salt solution-perfused (PSS) rabbit lungs, decreased total and upstream (arterial) PVR, a response inhibited by NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). In lungs perfused with PSS containing RBCs, L-NAME increased total and upstream PVR. In lungs perfused with PSS containing glibenclamide-treated RBCs, which inhibits ATP release, L-NAME was without effect. Apyrase grade VII (8 U/ml), which degrades ATP to AMP, was without effect on PVR in PSS-perfused lungs. These results are consistent with the hypothesis that ATP, released from RBCs as they traverse the pulmonary circulation, evokes endogenous NO synthesis.
authors.affiliation: Department of Pharmacological and Physiological Science, School of Medicine, Saint Louis University, 1402 South Grand Blvd., St. Louis, MO 63104, USA. spraguer@slu.edu
authors.forename: Randy S
authors.initials: RS
authors.lastname: Sprague
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Olearczyk
authors.forename: Dana M
authors.initials: DM
authors.lastname: Spence
authors.forename: Alan H
authors.initials: AH
authors.lastname: Stephenson
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sprung
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lonigro
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001081:Apyrase / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004907:Erythrocyte Deformability / Q000187:drug effects; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008168:Lung / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D012492:Salts / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D012492:Salts; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D001081:Apyrase; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester