Clinical and experimental studies on guanidino compounds in uremia

1) Eleven guanidino compounds were successively isolated and determined in uremic serum and brain by liquid chromatography using the cation-exchange resin (LCR-2, Jelco) and selecting the proper buffer system for elution. 2) The concentration of total guanidino compounds, including arginine, taurocyamine, glycocyamine, and guanidinosuccinic acid etc., was 143±39nmoles/ml in normal human serum (BUN:7-20mg/dl). 3) The concentration of total guanidino compounds was 296±101nmoles/ml in serum of uremic patient (BUN: 40-161mg/dl). The concentration of taurocyamine and guanidinosuccinic acid were significantly elevated and methylguanidine was detectable in uremic serum. 4) Experimental uremia was induced by bilateral ureteral ligation of rabbit. Forty-eight hours after ligation when blood urea level rose to 90-219mg/dl, the concentration of guanidino compounds, especially taurocyamine and guanidinosuccinic acid, significantly increased. 5) The concentration of total guanidino compounds in norlnal rabbit brain was 359±37nmoles/g and that of γ-guanidino-β-hydroxybutyric acid and γ- guanidinobutyric acid were much higher than in serum. At forty-eight hours after bilateral ureteral ligation, significant increment of taurocyamine and decrease of glycocyamine and arginine were noted. The trace amount of methylguanidine was detected. 6) Generalized tonic and clonic convulsion was observed in the rabbit three minutes after intracisternal injection of methylguanidine (1.5mg/kg b. w.). Seizure discharges were recorded on electrocorticogram of the rabbit and cat, and it was comfirmed that spike activity originated in hippocampus on depth recordings.