166 PROTECTIVE EFFECT ON ATRIAL NATRIURETIC PEPTIDE (AND) ON CELLS DAMAGED BY HYPOXIA OR OXYGEN RADICALS

Abstract

Recent reports1,2 show that ANP attenuates acute ischemic renal failure (ARF) in vivo and in isolated perfused kidney. ANP is a potent renal vasodilator, and the protective effect of ANP was shown to be mediated by improving hemodynamics. To determine if ANP also has a protective effect at the cellular level, studies were performed in hepatocyte cell cultures, also known to respond strongly to ANP. Cells were exposed to A) 0.5% O2 for 4 h and reoxygenation at 20% O2 for 20 h or B) hypochlorous acid (100 μM) for 1 h. Both procedures are known to lead to the production of free radical metabolites, which cause cell damage. In response, hepatocytes showed increased membrane lesions (assessed by release of serum glutamate transaminase, bleb formation and non-exclusion of trypan blue) and proteolysis (assessed by the decrease of trichloroacetic acid-precipitable (14Clvaline-labeled peptides). ANP (0.01,0.1 and 1 μM) given at any time during the experiment. Protected the cells against further membrane damage and proteoysis or, at least, attenuated these processes. This cytoprotective effect of ANP was paralleled by an up to 3-fold increase in cellular cGMP content. Both cytoprotection and the increase in cGMP could be blocked by pertussis toxin, which strongly suggests that the ANP-particulate guanylate cyclase response is mediated by a G-protein in hepatocytes. Sodium nitroprusside. which also increased the cells cGMP content via cytosolic guanylate cyclase, had a cytoprotective effect similar to ANP. These results show that the beneficial effect of ANP in ARF may not only be hemodynamically mediated but can also be the result of cytoprotective properties. Furthermore these results stress the possible importance of cGMP and cGMP-mediated response in cytoprotection. )1,)2 J.Clin.Invest. 80(1987). 698, 1232