RENAL EFFECTS OF CONCURRENT E-24.11 AND ACE-INHIBITION IN THE AORTO-VENOCAVAL FISTULA RAT

1 The present studies compare the early renal response to (a) an endop eptidase-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 mode l 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 e xcretion without affecting significantly blood pressure or glomerular filtration rate (GFR). 3 Lisinopril (0.03 mg kg(-1)) alone inhibited t he presser 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 candoxa trilat (3 mg kg(-1)) and the associated rise in urinary cyclic GMP, bu t sodium excretion eventually reached levels associated with acute E-2 4.11 inhibition. 5 Doses of the dual E-24.11/ACE inhibitor, sampatrila t, that inhibited the presser response to angiotensin I reduced mean a rterial blood pressure and produced a delayed natriuresis and rise in urinary cyclic GMP excretion when compared to candoxatrilat alone. 6 C oncurrent administration of an ACE inhibitor reduces the early renal r esponse to E-24.11 inhibition in the A-V fistula rat, an effect attrib utable to the hypotensive action of this combination.