The atriopeptidase inhibitor (+/-) candoxatrilat reduces the clearance of atrial natriuretic factor in both intact and nephrectomized rats: evidence for an extrarenal site of action

P L Barclay; J A Bennett; G M Samuels; N B Shepperson

doi:10.1016/0006-2952(91)90091-i

The atriopeptidase inhibitor (+/-) candoxatrilat reduces the clearance of atrial natriuretic factor in both intact and nephrectomized rats: evidence for an extrarenal site of action

Biochem Pharmacol. 1991 Mar 1;41(5):841-4. doi: 10.1016/0006-2952(91)90091-i.

Authors

P L Barclay¹, J A Bennett, G M Samuels, N B Shepperson

Affiliation

¹ Department of Cardiovascular Biology, Pfizer Central Research Sandwich Kent, U.K.

PMID: 1847819
DOI: 10.1016/0006-2952(91)90091-i

Abstract

We have demonstrated that in anaesthetized rats. (+/-) candoxatrilat reduces the clearance of both 125IANF and ANF 5-28, and prolongs the elimination half-life. These effects occur independent of glomerular filtration, since they are not attenuated by nephrectomy. Moreover, they cannot be attributed to blockade of ANF-C receptors. Our findings suggest that (+/-)candoxatrilat exerts its activity in vivo by specific inhibition of atriopeptidase at both renal and extra-renal locations.

MeSH terms

Animals
Atrial Natriuretic Factor / blood
Atrial Natriuretic Factor / pharmacokinetics*
Carbamates / pharmacology*
Cyclohexanecarboxylic Acids*
Enzyme Inhibitors / pharmacology
Half-Life
Kidney / drug effects*
Kidney / metabolism
Kidney Glomerulus / metabolism
Male
Nephrectomy
Peptide Fragments / pharmacokinetics
Propionates / pharmacology*
Rats
Rats, Inbred Strains
Receptors, Cell Surface / metabolism

Substances

Carbamates
Cyclohexanecarboxylic Acids
Enzyme Inhibitors
Peptide Fragments
Propionates
Receptors, Cell Surface
candoxatrilat
Atrial Natriuretic Factor
atrial natriuretic factor (5-28)