Endothelial Angiotensin-Converting Enzyme and Neutral Endopeptidase in Isolated Human Umbilical Vein: An Effective Bradykinin Inactivation Pathway

NOWAK W, ERRASTI AE, ARMESTO AR, SANTíN-VELAZQUE LN, ROTHLIN RP.

EUROPEAN JOURNAL OF PHARMACOLOGY

ELSEVIER SCIENCE BV

Año: 2011 vol. 667 p. 271 - 277

0014-2999

Kinins are metabolized by metallopeptidases present in different tissues. The aimof this study was to evaluate, employing functional studies in isolated humanumbilical vein, the possible participation of angiotensin-converting enzyme,neutral endopeptidase and aminopeptidase P as an inactivation pathway ofbradykinin, as well as assess if the endothelial layer is involved in thisprocess. Concentration-response curves to bradykinin were constructed after 120min incubation period on human umbilical vein rings with and without endothelium and enzymatic inhibitors were applied 30 min before construction ofconcentration-response curves. The presence of endothelium was confirmed byhistological studies. Bradykinin-induced contractile responses were potentiatedin human umbilical vein without endothelium when compared to intact tissues.Application of captopril 1 μM (angiotensin-converting enzyme inhibitor) orphosphoramidon 10 μM (neutral endopeptidase inhibitor) induced a leftward shiftof bradykinin-elicited responses in human umbilical vein with endothelium whileno effect was observed in tissues denuded of endothelium under the sametreatment. Exposure to apstatin 10 μM (aminopeptidase P inhibitor) did notpotentiate bradykinin-induced effects in intact human umbilical vein. Whenangiotensin-converting enzyme and neutral endopeptidase were concomitantlyinhibited, there was a higher potentiation of bradykinin-elicited responsescompared to the effects observed under individual inhibition of either enzyme.Moreover, concentration-response curves to FR190997, a non-peptidic bradykininB(2) receptor agonist, were not modified under dual enzymatic inhibition. Inconclusion, our results demonstrate for the first time the functional relevanceof angiotensin-converting enzyme and neutral endopeptidase, localized on theendothelial layer, acting concurrently as a bradykinin inactivating pathway inisolated human umbilical vein.