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J L Prado

Publications and source records attributed to J L Prado.

32 records · Page 2Linked to original sources
PubMed1976

Catabolism of vasoactive polypeptides by perfused rat liver.

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.

Angiotensin II↗
PubMed1975

Recovery and conversion of kinins in exsanguinated rat preparations.

A rat preparation in which the perfusion route bypassed the lungs, which were substituted by an artificial oxygenator, was exsanguinated and perfused with oxygenated 4% dextran (M.W. 70,000) in Tyrode's fluid; a peristaltic pump propelled the perfusing fluid at 20-25 ml/min through the aortic arch and the perfusion medium returned to the right ventricle. Known amounts of bradykinin (BK), kallidin (lysul-bradykinin, LBK) and methionyllysylbradykinin (MLBK) were administered as single injections and samples of the perfusion fluid removed between 1.5 to 6 min following injection. Average total kinin activity remaining in the circulating fluid was calculated from assays on the isolated guinea pig ileum against respective kinin injected and found to be after 3 and 6 min respectively: 20 and 5% for BK, 54 and 21% for LBK, 60 and 30% for MLBK. When the lungs were introduced in the perfusion circuit BK recoveries decreased to 0.4% at 4 min and 0% at 6 min. In 2 experiments 1 mg MLBK and, in another two, 1 mg of LBK were recirculated for 3 to 3.5 min in the rat preparation with lung bypass; enzymic reactions were interrupted in the perfusates after removal by lowering the pH to 4.7 and placing them in a boiling water bath for 5 min. Following proper dilution, kinin activity left in the perfusates was separated on carboxymethylcellulose columns; in 3 experiments about 50% of the activity was identified as BK from its elution position and resistance to trypsin digestion. The average BK-inactivating potency of the perfusate obtained from the rat with lung bypass was 0.3 mug BK/min x ml compared to 16 mug BK/min x ml of rat plasma. The arylamidase activity on arginylnaphthylamide of the perfusate was 2 n moles NA/min x ml and it was about 25-fold lower than that of rat plasma. Rat liver was exsanguinated and perfused in situ through the portal vein and inferior cava vein using the same conditions as for the whole animal. The perfusion rate was 12 ml/min. The recovery of injected BK in this preparation was 40% after 2 min of recirculation, declining progressively in the following minutes. When MLBK was perfused in this preparation for 3 min or glycylarginyllysylbradykinin (GALBK) for 3 and 5 min, significant amounts of BK were found in the perfusates. We conclude that LBK, MLBK and GALBK may be converted at a high rate into BK by tissue aminopeptidases found in the rat preparations used. BK inactivation in the whole rat is a fast reaction, even when the pulmonary tissue is not involved in the inactivation.

Aminopeptidases↗