Neutral endopeptidase upregulation in isolated human umbilical artery: involvement in desensitization of bradykinin-induced vasoconstrictor effects.

PELOROSSO F, HALPERIN A, PALMA A, DIANA MENENDEZ S, GAGLIARDO M, HITA F, ROTHLIN R.

cordoba, Hotel ACA, Argentina.

Congreso; XXXVIII REUNION ANUAL DE LA SOCIEDAD ARGENTINA DE FARMACOLOGÍA EXPERIMENTAL; 2006

SOCIEDAD ARGENTINA DE FARMACOLOGÍA EXPERIMENTAL

Introduction: Bradykinin (BK) prod- uces constriction ofhuman umbilical artery (HUA) with high potency andefficacy. The objective of the present study was to evaluate therole of two known BK-inactivating enzymes, angiotensinconverting enzyme (ACE) and neutral endopeptidase (NEP),as a function of in vitro incubation time isolated HUA.Methods and results: Concentration response curves tobradykinin after a 2 h incubation failed to be modified by 1μM captopril (ACE inhibitor) or 10 μM phosphoramidon(NEP inhibitor). However, BK-elicited responses at 5 h werepotentiated when tissues were exposed to captopril orphosphoramidon. In addition, the potency of control responseselicited by BK at 5 h was significantly lower than thatobserved at 2 h. NEP activity determined in tissues incubatedduring 5 h showed an increase over activity in 2 h and nonincubatedtissues. Moreover, tissue incubation with 10 μMcycloheximide reversed the activity increase observed at 5 h.Furthermore, Western blot experiments in HUA whole cellextracts showed a single 100 KDa band corresponding to NEP.Densitometric analysis revealed that NEP content in HUA at 5h was higher than in 2 h-incubated and non-incubated tissues.Conclusion: The results suggest that NEP is up-regulated inHUA after prolonged in vitro incubation and is involved indesensitization of bradykinin-induced vasoconstrictor effectsin HUA.