Human pepsinogens, the precursors of pepsin, originating from the stomach mucosa, are classified into two biochemically distinct groups, namely pepsinogen I (PG I) and pepsinogen II (PG II). We studied the serum levels of PGI and II in 51 normal volunteers, 23 chronic glomemlonephritis patients, 21 continuous ambulatory peritoneal dialysis (CAPD) patients and 40 hemodialysis patients. Serum pepsinogen levels were measured with a competitive binding double antibody radioimmunoassay. In the group of chronic glomemlonephritis patients, a positive correlation between the serum creatinine and the pepsinogen levels were found. The serum pepsinogen levels were remarkably elevated in CAPD and hemodialysis patients. The median levels of post-hemodialysis PGI(265.4 ± 165.2 ng/ml) and PG II (41.7 ± 38.0 ng/ml) were significantly higher than prehemodialysis values (PG I 207.4 ± 127.5 ng/ml, PG II 29.0 ± 16.6 ng/ml). Pepsinogen release by isolated gastric glands of guinea pigs was suppressed by guanidinosuccinic acid and was facilitated by calcium. The data suggest that both removal of guanidinosuccinic acid and infusion of calcium during hemodialysis contribute to the raised serum levels of these pepsinogens after hemodialysis.

Background: The L-arginine-nitric oxide (NO) pathway plays an important role in the modulation of glomerular disease. We investigated whether β-blocking agents, with and without an NO-generating function, had renoprotective effects in the 5/6 nephrectomized rats (Nx), an animal model of glomerulosclerosis. Methods: Nipradilol, a β-blocker with an ONO₂ group (5, 10 or 15 mg/kg/day) and propranolol, a β-blocker without this group (50 mg/kg/day) were administered for 12 weeks to Nx together with and without nitro-L-arginine methyl ester (L-NAME). We evaluated the effects of both drugs on proteinuria, hypertension, renal function, glomerulosclerosis and urinary excretion of NO metabolites (U_NOx) and cyclic GMP (U_cGMP). Results: Both drugs similarly attenuated the elevated blood pressure in Nx. However, nipradilol, at doses of 10 and 15 mg/kg/day, significantly decreased proteinuria and glomerulosclerosis, while propranolol did not. Nx showed reduced U_NOx in comparison with the sham-operated rats. Nipradilol increased U_NOx and U_cGMP significantly and in a dose- dependent manner, whereas propranolol reduced them to levels lower than those in Nx. Nx receiving L-NAME reduced U_NOx. The addition of nipradilol increased U_NOx and decreased urinary protein excretion and glomerulosclerosis, suggesting that the NO released from the drug contributed to its renoprotective effect. Conclusion: These findings indicate that nipradilol exerts its renoprotective effect through NO generation, and not by lowering blood pressure. The β-adrenergic blocking action per se does not seem to be related to the renoprotective effect of these agents.

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