Effect of endopeptidase-24.11 inhibition and of atrial natriuretic peptide clearance receptor ligand on the response to rat brain natriuretic peptide in the conscious rat.
1. The present studies examined the effect of (a) a specific endopeptidase-24.11 (E-24.11) inhibitor (candoxatrilat) and (b) a ligand for the atrial natriuretic peptide (ANP) clearance receptor (SC 46542) on the renal and blood pressure response to brain natriuretic peptide (BNP) in conscious rats. 2. Infusion of BNP 200 ng kg-1 min-1 for 60 min produced a small rise in urinary sodium and guanosine 3':5'-cyclic monophosphate (cyclic GMP) excretion with a non-significant fall in mean arterial blood pressure. 3. Candoxatrilat (3 mg kg-1) alone had no significant effect on sodium excretion or blood pressure but markedly potentiated the natriuretic response to BNP. 4. Similarly SC 46542 (68 micrograms kg-1; 6.8 micrograms kg-1 min-1) which produced no significant effect on its own, potentiated the natriuresis-induced by BNP, although the effect was of shorter duration compared to that of candoxatrilat. 5. The data indicate two approaches to the potentiation of the renal activity of BNP and suggest that BNP may mediate some of the activity of E-24.11 inhibitors reported in cardiac failure.
Kirk
J E
JE
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London.
Wilkins
M R
MR
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000493:pharmacokinetics; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000652:urine; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects; D008024:Ligands; D008297:Male; D020097:Natriuretic Peptide, Brain; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D010446:Peptide Fragments / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D017461:Receptors, Atrial Natriuretic Factor / Q000187:drug effects*; D012964:Sodium / Q000652:urine
D003509:Cyclohexanecarboxylic Acids; D004232:Diuretics; D008024:Ligands; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D020097:Natriuretic Peptide, Brain; C059320:SC 46542; C073021:brain natriuretic peptide-45; C060942:candoxatrilat; D009320:Atrial Natriuretic Factor; D012964:Sodium; D015260:Neprilysin; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP