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

Abstract

The influence of some peptidase inhibitors on oedema and plasma extravasation induced by bradykinin and carrageenan in rat paw was evaluated. 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 M), 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 M). It was not modified by mergepta (10⁻⁴ M), phosphoramidon (10⁻⁵ M) and diprotin A (10⁻³ M). Des-Argl-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-deficient Brown Norway rats. Angiotensin-converting enzyme and amino-peptidase 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.