Effects of the dual metallopeptidase inhibitor, MDL 100,240, on regional haemodynamic responses to vasoactive peptides in conscious rats

British Journal of Pharmacology
S M GardinerT Bennett

Abstract

1. The effects of combined inhibition of neutral endopeptidase 24.11 and angiotensin-converting enzyme, with the dual metallopeptidase inhibitor, MDL 100,240 (3 mg kg-1 bolus, 3 mg kg-1, h-1 infusion), on baseline haemodynamics and on responses to a variety of vasoactive peptides were studied in conscious Long Evans rats (350-450 g: n = 9) chronically instrumented for the assessment of regional haemodynamics. 2. The experiments ran over 4 consecutive days. On the first 2 days the animals received the vehicle for MDL 100,240, and were given bolus i.v. injections of angiotensin I (AI; 250 pmol kg-1), angiotensin II (AII; 125 pmol kg-1), bradykinin (BK: 3 nmol kg-1) and endothelin-1 (ET-1; 250 pmol kg-1) on one day and AI (as above), atrial natriuretic peptide (ANP: 500 pmol kg-1) and big endothelin-1 (big ET-1; 500 pmol kg-1) on the other day in a random manner. On the third and fourth experimental days the vasoactive peptides were given in the same order as before, but in the presence of MDL 100,240. 3. Thirty minutes after onset of administration of vehicle, on the first or second experimental day, there were no consistent cardiovascular changes. However, at the same time following onset of MDL 100,240 administration on the thi...Continue Reading

References

Jul 1, 1995·Journal of Cardiovascular Pharmacology·J F FrenchR C Dage
Oct 14, 1994·Biochemical and Biophysical Research Communications·S De LombaertR L Webb
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·M C Fournié-ZaluskiJ B Michel
Sep 1, 1993·British Journal of Pharmacology·S M GardinerT Bennett
Jan 1, 1988·Neurochemistry International·G M LittlewoodA J Turner

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Citations

Mar 6, 2004·Clinical and Experimental Hypertension : CHE·Sally A MifsudJennifer L Wilkinson-Berka
May 18, 2004·Journal of Clinical Pharmacology·Marc PfisterJeffrey S Barrett
Feb 22, 2003·Cardiovascular Drug Reviews·Gian Paolo Rossi

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