L-ARGININE REDUCES KIDNEY COLLAGEN ACCUMULATION AND N-EPSILON-(CARBOXYMETHYL)LYSINE IN THE AGING NMRI-MOUSE

Background. The aging process leads to glomerular basement membrane (G BM) thickening due to increased collagen accumulation. This mechanism can be explained by the nonenzymatic glycosylation hypothesis of colla gen aging. We have published the positive effect of L-arginine on gluc ose-mediated cross-linking, and if the nonenzymatic glycosylation hypo thesis of aging holds, the pharmacological effect of L-arginine on glu cose-mediated cross-links in the aging Hannover NMRI mouse can be expe cted. Methods. Animals were given L-arginine 50 mg/kg body weight/day orally and compared to a control group without treatment. Results. Ele ctron microscopical measurement of the GBM thickness showed significan t differences between controls (4920 +/- 1680 A) and the experimental group (2345 +/- 815 A). Determination of the total kidney collagen con tent based upon 4-trans hydroxyproline revealed 13.9 +/- 3.9 mg/100 mg kidney weight (kw) in the untreated group versus 7.9 +/- 4.2 mg100 mg kw in the treated group. For solubility studies based upon hydroxypro line determination, collagen was eluted by pepsin digestion. This reve aled 18.7 +/- 3.9 mg/100 mg kw in the controls versus 7.8 +/- 4.8 mg/1 00 mg kw in the treated group. HPLC analysis of N-epsilon-(carboxymeth yl)lysine (CML) showed in the treated group (1.847 +/- 0.247 nM/mu M h ydroxyproline) significantly lower concentrations than in the untreate d group (3.399 +/- 0.349 nM/mu M hydroxyproline). On sodium dodecyl su lfate (SDS) polyacrylamidegel electrophoresis, the eluates of the trea ted animals showed less high molecular weight material than their untr eated mates. Conclusions. We cannot discriminate between the probable mechanisms of cross-linking but we clearly can state that L-arginine r educes cross-linking and collagen accumulation in aging collagen type IV accompanied and strongly associated with decreased CML content.