title: Protective effect of alpha-human atrial natriuretic polypeptide (alpha-hANP) on chemical-induced pulmonary edema.
abstract: It has been established that alpha-hANP, the newly discovered peptide extracted from human cardiac atria, has potent natriuretic and hypotensive actions. Our present investigation is the first to demonstrate that alpha-hANP is capable of protecting against pulmonary edema caused by various chemicals, using isolated perfused guinea pig lung system. Lungs were perfused via pulmonary artery with Krebs-Ringer bicarbonate buffer at 5.0 ml/min, and wet weight of lungs and perfusion pressure of pulmonary artery (Pa) were monitored. Bolus injection of Triton-X or CHAPS into cannulated pulmonary artery produced edema as indicated by a massive increase in wet weight and a slight increase in Pa. Constant infusion of alpha-hANP through pulmonary artery at 200 ng/ml was effective in causing decrease in wet weight of lung. Perfusion of lung with paraquat or PGF2 alpha, and repeated bolus injection of arachidonic acid or PGE2 caused elevation in both wet weight of lung and Pa. The treatment with alpha-hANP similar to that described above also protected against edema caused by paraquat or arachidonic acid. Bolus administration of epinephrine induced a slight increase in wet weight and Pa, and alpha-hANP was effective in decreasing the elevated lung wet weight and Pa of lungs. Infusion or bolus administration of alpha-hANP into control lungs increased cGMP level in outflow perfusate as well as in lung tissue significantly. In lungs with edema which were induced by Triton-X or paraquat, there was a slight increase in cGMP level in Triton-X treated and no increase in paraquat treated lung tissues. In either cases, was there any increase in cGMP level in perfusate. The specific binding study of [125I]alpha-hANP revealed that the lack of increase in cGMP was not due to a loss of receptor in Triton-X or paraquat treated lungs. Thus our study demonstrated that alpha-hANP had a direct anti-edematic action(s) in lung which was not secondary to the systemic natriuretic and/or hypotensive action(s).
authors.affiliation: University of California, Riverside 92521.
authors.forename: T
authors.initials: T
authors.lastname: Imamura
authors.forename: N
authors.initials: N
authors.lastname: Ohnuma
authors.forename: F
authors.initials: F
authors.lastname: Iwasa
authors.forename: M
authors.initials: M
authors.lastname: Furuya
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: N
authors.initials: N
authors.lastname: Inomata
authors.forename: T
authors.initials: T
authors.lastname: Ishihara
authors.forename: T
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids; D009320:Atrial Natriuretic Factor / Q000494:pharmacology / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D002793:Cholic Acids; D006152:Cyclic GMP / Q000378:metabolism; D015237:Dinoprost; D015232:Dinoprostone; D004837:Epinephrine; D006168:Guinea Pigs; D006801:Humans; D007201:Indicator Dilution Techniques; D008168:Lung / Q000473:pathology; D008297:Male; D009638:Norepinephrine; D017830:Octoxynol; D009929:Organ Size / Q000187:drug effects; D010269:Paraquat; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology*; D011092:Polyethylene Glycols; D011458:Prostaglandins E; D011460:Prostaglandins F; D011651:Pulmonary Artery; D011654:Pulmonary Edema / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
chemical_list: D001095:Arachidonic Acids; D002793:Cholic Acids; D010446:Peptide Fragments; D011458:Prostaglandins E; D011460:Prostaglandins F; D016718:Arachidonic Acid; D011092:Polyethylene Glycols; D009320:Atrial Natriuretic Factor; D017830:Octoxynol; D015237:Dinoprost; D006152:Cyclic GMP; D015232:Dinoprostone; D010269:Paraquat; C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate; D009638:Norepinephrine; D004837:Epinephrine