Peptides that display bradykinin-potentiating activity have been obtained from a number of distinct sources, such as snake venoms, fibrinogen, and casein. This paper describes the isolation and sequencing of a novel bradykinin-potentiating peptide, generated by tryptic hydrolysis of the gamma-casein chain. No homology was found to other known vasoactive or vasopotentiating peptides. The octapeptide Tyr-Pro-Val-Gln-Pro-Phe-Thr-Glu, corresponding to the gamma-casein(114-121) sequence, was isolated from the tryptic hydrolysis of gamma-casein and also synthesized by solid-phase peptide synthesis. Both natural and synthetic peptides had the same retention time in HPLC and displayed a selective potentiating activity on isolated guinea-pig ileum for bradykinin and Lys-bradykinin but were not able to potentiate the effects of Met-Lys-bradykinin, Ile-Ser-bradykinin, angiotensin II, acetylcholine, or histamine. Intravenous injections of bradykinin and of bradykinin-potentiating octapeptide produced a persistent hypotension in conscious rats, a pattern that was not obtained when the octapeptide was replaced by captopril. This bradykinin-potentiating octapeptide is a strong competitive inhibitor of endo-oligopeptidase A (EC 3.4.24.15, formerly EC 3.4.22.19), but it has low inhibitory potency towards angiotensin-converting enzyme (EC 3.4.15.1). Thus, our results suggest that other peptidases in addition to angiotensin-converting enzyme, such as endo-oligopeptidase A, may contribute to the reduction of the effective concentration of bradykinin in the circulation.

It is well known that the blood fibrinogen is highly increased after trauma (Chanutin, Hortensstine, Cole and Ludewig, 1938). Henriques, Henriques and Selye (1950) observed that this response to trauma is significantly smaller in the adrenalectomized rat.It seems obvious that in the normal rat the fibrinogen response to trauma could depend on the presence of the adrenal cortex, the adrenal medulla or both. The first possibility is suggested by the knewn fact that cortical hormones influence protein metabolism (Forsham, Thorn, Bergner and Emerson, 1946;Ingle and Prestrud, 1948;Engel, Schiller and Pentz, 1949) while the role of the adrenal medulla is indicated by the fact that epinephrine injections cause an increase in fibrinogen (Henriques, Henriques and Mattos, 1950).We therefore decided to study the effect of trauma upon blood fibrinogen in adrenal demedullated rats. MATERIAL AND METHODSFour groups of male Wistar rats, weighing 100 to 150 gm. were used in this experiment. In group I adrenal enucleation was performed, group II was totally adrenalecto-

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