title: Atrial natriuretic peptide protects hepatocytes against damage induced by hypoxia and reactive oxygen. Possible role of intracellular free ionized calcium.
abstract: Elevated concentrations of atrial natriuretic peptide reportedly mitigate acute renal failure in vivo and in the isolated perfused kidney (M. Nakamoto, J.I. Shapiro, P.F. Shanley, L. Chan & R.W. Shrier (1987) J. Clin. Invest. 80, 698-705; S.G. Shaw, J. Weidmann, J. Hodler, A. Zimmermann & A. Paternostro (1987) J. Clin. Invest. 80, 1232-1237). Since atrial natriuretic peptide has been shown to be a potent vasodilator, this beneficial effect may be due entirely to improved haemodynamics. To determine whether atrial natriuretic peptide also has a protective effect at the cellular level, rat hepatocyte cell cultures were treated with atrial natriuretic peptide prior to or after induction of cell damage by hypoxia (0.5% O2 for 4 h) or reactive oxygen (hypochlorous acid). Bleb formation, degradation of radiolabeled trichloroacetic acid-precipitable peptides, release of lactate dehydrogenase and trypan blue exclusion were used as indicators of cell damage. Atrial natriuretic peptide treatment distinctly protected the cell cultures against damage in both cases. This beneficial effect of atrial natriuretic peptide was partly mimicked by sodium nitroprusside, which, like atrial natriuretic peptide, largely increased the cellular cGMP content. 6-Anilino-5,8-quinolinedione (Ly 83583), an inhibitor of particulate guanylate cyclase, blocked the protective effect of atrial natriuretic peptide. Therefore a cGMP-mediated mechanism seems to be involved in the cytoprotective action of atrial natriuretic peptide. Fluorometric measurements using the Ca2+-sensitive dye Quin-2 showed that the elevation of intracellular Ca2+ after cellular insult by hypochlorous acid is prevented by atrial natriuretic peptide. These results suggest that atrial natriuretic peptide may attenuate hypoxic and toxic cell damage by increasing cGMP and reducing intracellular Ca2+.
authors.affiliation: Institut für Klinische Biochemie, Universität Bonn, F.R.G.
authors.forename: A A
authors.initials: AA
authors.lastname: von Ruecker
authors.forename: M
authors.initials: M
authors.lastname: Wild
authors.forename: G S
authors.initials: GS
authors.lastname: Rao
authors.forename: F
authors.initials: F
authors.lastname: Bidlingmaier
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000032:analysis / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006997:Hypochlorous Acid / Q000009:adverse effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D000634:Aminoquinolines; D009599:Nitroprusside; D006997:Hypochlorous Acid; D009320:Atrial Natriuretic Factor; C041715:6-anilino-5,8-quinolinedione; D000242:Cyclic AMP; D006152:Cyclic GMP; D010100:Oxygen; D002118:Calcium