The intestinal absorption of small peptides was investigated in rats under unrestrained conditions. The peptide utilized in the experiment was hydrolysate of egg white protein with an average molecular weight of about 350 and containing less than 10% of free amino acids. We compared the intestinal absorption of these small peptides with that of an amino acid mixture with the same small peptide amino acid composition by determining the concentration of individual amino acids in portal blood after a single administration of a nitrogen source. The absorptive intensity of each amino acid was calculated from its rate of elevation in the portal blood; it was higher in the small peptides. The proportion of the amount of each amino acid absorbed in portal blood from small peptides was much more like the composition of the administered amino acids than like that from the amino acid mixture. Among the amino acids administered in the mixture, some amino acids such as L-tyrosine, L-threonine, L-serine and L-histidine increased more slowly in the blood than others. These results suggested that the small peptide formula was utilized more effectively than the amino acid mixture and had higher nutritive value.

To further elucidate the natriuretic mechanisms of neutral endopeptidase 24.11 (NEP) inhibition, we employed a new specific NEP inhibitor, UK 73967 (UK), with or without a specific kinin receptor antagonist, Hoe 140 (Hoe), in Sprague-Dawley rats, and evaluated the renal NEP, kinins and plasma ANP simultaneously. There were no significant changes in urinary NEP, kinins, urine volume (UV) or urinary sodium excretion (UNaV) with vehicle treatment in anesthetized normotensive rats. Infused UK (10 mg/kg) significantly decreased NEP, and increased kinins, UV and UNaV. There was not a significant difference in plasma ANP between the vehicle and UK groups. Simultaneous administration of Hoe (20 nmol/kg) canceled the increases of UV and UNaV caused by UK. From these results, we conclude that inhibition of NEP may exaggerate the contribution of renal kinins to the renal water-sodium metabolism and overcome the contribution of ANP on that metabolism at least in normotensive rats.

To further elucidate the renal effects of NEP inhibition, we employed NEP inhibitor UK 73967 (UK), with or without a kinin receptor antagonist Hoe 140 (Hoe), in Sprague-Dawley normotensive rats and DOCA-salt hypertensive rats. In Sprague-Dawley rats: 1) injected UK significantly decreased NEP, and increased kinins, urine volume (UV) and urinary sodium excretion (UNaV), while none of the variables changed with vehicle treatment; 2) no difference was found in plasma ANP between the vehicle and UK groups; and 3) Hoe canceled the increases of UV and UNaV caused by UK. In DOCA-salt rats: 1) infused UK significantly decreased NEP, and increased UV and UNaV, while UV and UNaV were slightly decreased, and NEP did not change with vehicle treatment; 2) plasma ANP was significantly higher in UK group than in the vehicle group; and 3) Hoe could not abolish the increase of UV and UNaV induced by UK. These data indicate that the contributions of renal kinins and plasma ANP to the diuretic and natriuretic mechanisms of NEP inhibition may differ between Sprague-Dawley normotensive rats and DOCA-salt hypertensive rats.

To further clarify the significance of renal kininases in patients with Cushing's syndrome, daily urinary excretions of total kininase, kininase I, Ii and neutral endopeptidase 24.11 (NEP) were examined and evaluated for the relations between plasma cortisol level and these kininases. Urinary total kininase kininase I, II and NEP were significantly higher in patients with Cushing's syndrome than in normotensives. There was a significant positive correlation between plasma cortisol level and total kininase or NEP, and the same tendency was observed between plasma cortisol level and kininase I. After adrenalectomy, urinary kininases decreased to normal levels. These findings suggested that: 1) kininase I, II and NEP are accelerated in Cushing's syndrome; 2) glucocorticoids may regulate renal kininases; and 3) accelerated renal kininases may play some role in disorders of the renal water-sodium metabolism and in high blood pressure in Cushing's syndrome.