Exsanguinated rat liver preparations perfused in situ with oxygenated saline solutions inactivated recirculating bradykinin (BK) at rates of 2.3 to 9.1 and isoleucyl5 angiotensin II (AII) at rates of 2.8 to 15.0 nmoles X min-1 X g-1 of liver, depending on the initial concentration of the peptides in the perfusion fluid (3.1 to 18.9 X 10(-6) M for BK and 8.5 to 17.0 X 10(-6) M for AII). On the other hand, at similar concentrations, recirculation of isoleucyl5 Angiotensin I (AI) for 8 min did not lead to decrease of its biological activity when assayed on the isolated rat uterus. Following a single passage through liver, picomole amounts of both BK and AII were inactivated by about 90% as revealed by assays on a superfused rat uterus. The potency ratio AI:AII, assayed on a superfused rat uterus was 1:22 and changed to 1:5 following a single passage of both peptides through liver. This finding and the separation of 4.9% of AII on carboxymethylcellulose columns following recirculation of AI through rat liver indicate a conversion of AI into AII. The dipeptides Phe-Arg, Ser-Pro and Gly-Phe were identified among the hydrolysis products of perfused BK. A peptidyldipeptide hydrolase (EC 3.4.15) may be responsible for both the BK inactivation and AI conversion. The inactivation of AII cannot be attributed to the same enzyme.
The effect of an n-3 (fish) and n-6 (soybean) fatty acid-rich diet on carrageenin paw oedema in rats, and the participation of adrenal gland, corticosterone and α2-macroglobulin (α2-M) in this process were studied. A significant inhibition of carrageenin oedema was observed not only in rats fed a diet rich in fish oil but also in the soybean group. α2-M was not detectable before carrageenin injection, suggesting that this putative antiinflammatory factor does not participate in the observed anti-inflammatory effect. Corticosterone levels were higher in fat-fed than in control rats, before carrageenin stimulus and adrenalectomy abolished the anti-inflammatory response in fat-fed animals, showing the important role of the adrenocortical hormones in this process.
The effect of the acute-phase response on the clearance rate of plasma kallikrein by the exsanguinated liver was studied in three groups of rats: a control group and two other groups that received either turpentine or an endogenous pyrogen preparation. The plasma kallikrein clearance rates were significantly higher in both inflamed groups.
During the acute phase of the inflammatory process there is a characteristic increase in some plasma proteins called collectively acute phase reactants (APR) as well as in the levels of corticosteroids. A bacterial endotoxin (LPS) that induces a strong acute phase response, indicated by high levels of fibrinogen and haptoglobin, did not show this effect when administered to rats treated previously with metopyrone, a specific inhibitor of corticosteroid hormone synthesis. These results suggest that adequate levels of these hormones are important for the production of acute phase reactants.
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