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Renal effects of concurrent E‐24.11 and ACE inhibition in the aorto‐venocaval fistula rat
Author(s) -
Kirk Jane E.,
Wilkins Martin R.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15763.x
Subject(s) - lisinopril , natriuresis , endocrinology , medicine , renal function , blood pressure , renin–angiotensin system , chemistry , ace inhibitor , angiotensin converting enzyme , angiotensin ii , excretion , enzyme inhibitor , enalapril , renal sodium reabsorption , kidney , reabsorption , enzyme , biochemistry
1 The present studies compare the early renal response to (a) an endopeptidase‐24.11 (E‐24.11) inhibitor (candoxatrilat) (b) an angiotensin‐converting enzyme (ACE) inhibitor (lisinopril) and (c) the combination of endopeptidase‐24.11 and ACE inhibition in the rat A‐V fistula model of chronic volume overload. 2 Candoxatrilat (3 and 10 mg kg −1 ) i.v. produced a prompt 3 fold increase in urinary sodium and cyclic GMP excretion without affecting significantly blood pressure or glomerular filtration rate (GFR). 3 Lisinopril (0.03 mg kg −1 ) alone inhibited the pressor response to angiotensin I but had no significant effect on urinary sodium excretion or blood pressure. 4 Lisinopril (0.03 mg kg −1 ) attenuated significantly the early natriuretic response to candoxatrilat (3 mg kg −1 ) and the associated rise in urinary cyclic GMP, but sodium excretion eventually reached levels associated with acute E‐24.11 inhibition. 5 Doses of the dual E‐24.11/ACE inhibitor, sampatrilat, that inhibited the pressor response to angiotensin I reduced mean arterial blood pressure and produced a delayed natriuresis and rise in urinary cyclic GMP excretion when compared to candoxatrilat alone. 6 Concurrent administration of an ACE inhibitor reduces the early renal response to E‐24.11 inhibition in the A‐V fistula rat, an effect attributable to the hypotensive action of this combination.