Pharmacology
Original Paper
Acute Blood Pressure Effects of Selected Serine Proteases in Normotensive Rats and DogsWilliams J.C. · Falcone R.C. · Do M.L.T. · Lindstrom D.D. · Howe B.B.Department of Pharmacology, ICI Pharmaceuticals Group, ICI Americas Inc., Wilmington, Del., USA
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Article / Publication Details
Received: February 05, 1991
Accepted: April 11, 1991
Published online: June 06, 2008
Issue release date: 1991
Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 0
ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)
For additional information: https://www.karger.com/PHA
Abstract
The effects of bolus intravenous injections of various serine proteases (thrombin, trypsin, plasmin, neutrophil elastase and chymotrypsin) on arterial blood pressure were evaluated in anesthetized, normotensive rats. The activity to intravenous trypsin was also studied in anesthetized, normotensive dogs. In the rat, both thrombin (0.33–10 nmol/kg) and trypsin (4.2–420 nmol/kg) produced pronounced vasodepressor responses. The activity on blood pressure was observed immediately following injection of either protease, and both the magnitude and duration of the responses were dose dependent. Plasmin (37–350 nmol/kg) and neutrophil elastase (91–910 nmol/kg) also induced dose-dependent hypotension but at much higher dose levels. In addition, the magnitude of the blood pressure responses after plasmin and neutrophil elastase was less than those produced by thrombin and trypsin. Chymotrypsin, on the other hand, had a more diverse blood pressure profile. The protease induced a modest decrease in pressure at doses of 40 and 120 nmol/kg, a pressor response after 400 and 1,200 nmol/kg and at the highest dose tested (4,000 nmol/kg) profound hypotension. In the dog, trypsin produced a dose-dependent vasodepressor response similar to that observed in the rat. The doses of proteases producing alterations of blood pressure in the rat correlated inversely with the ability of rat serum or plasma to completely inhibit those proteases. The pharmacology of the trypsin or thrombin blood pressure response suggests the requirement of specific active enzymes to mediate the vasodepression induced by both proteases.
© 1991 S. Karger AG, Basel
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Article / Publication Details
Received: February 05, 1991
Accepted: April 11, 1991
Published online: June 06, 2008
Issue release date: 1991
Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 0
ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)
For additional information: https://www.karger.com/PHA
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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