Potentiation of the pro-inflammatory effects of bradykinin by inhibition of angiotensin-converting enzyme and aminopeptidase P in rat paws

Naunyn Schmiedebergs Arch Pharmacol. 1996 Nov;354(5):670-6. doi: 10.1007/BF00170844.

Abstract

The influence of some peptidase inhibitors on oedema and plasma extravasation induced by bradykinin and carrageenan in rat paw was evaluate. Bradykinin-induced oedema in normal rats was increased by o-phenanthroline (3.10(-2) M), by captopril (10(-6) M to 10(-4) M), by lisinopril (10(-6) M to 10(-4), or by lisinopril (10(-5) M) in combination with apstatin (8.10(-5) M or 1.4 10(-4) M). It was not modified by phosphoramidon (10(-6) M to 10(-5) M) and by diprotin A (10(-3) M). It was increased by mergepta at high concentrations (2.10(-4) M). Mergepta did not increase the potentiating effect of captopril. Carrageenan-oedema in normal rats was increased by captopril (10(-5) M), lisinopril (10(-5) M) and apstatin (1.4 10(-4) M. It was not modified by mergepta (10(-4) M), phosphoramidon (10 (-5) M) and diprotin A (109-3) M). Des-Arg1-bradykinin and Des-Arg9-bradykinin have low oedema-promoting effects. Captopril (10(-5) M) increased the effects of bradykinin but not those of carrageenan in kininogen-deficit Brown Norway rats. Angiotensin-converting enzyme and aminopeptidase P appear to be main kinin-inactivating enzymes in rat paws. Carboxypeptidase N, neutral endopeptidase 24.11 and dipeptidyl(amino)peptidase IV do not play a significant role in this inactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopeptidases / antagonists & inhibitors*
  • Aminopeptidases / pharmacology
  • Analysis of Variance
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Bradykinin / analogs & derivatives
  • Bradykinin / pharmacology*
  • Capillary Permeability / drug effects
  • Carrageenan
  • Edema / chemically induced*
  • Edema / metabolism
  • Excipients
  • Hindlimb / drug effects
  • Inflammation
  • Male
  • Organ Size / drug effects
  • Protease Inhibitors / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Excipients
  • Protease Inhibitors
  • Carrageenan
  • Aminopeptidases
  • X-Pro aminopeptidase
  • Bradykinin