Peptidase activities in rats treated chronically with N-omega-nitro-L-arginine methyl ester (L-NAME)

Autor(es)

Linardi, Alessandra ^[1] ; Panunto, Patricia Costa ; Ferro, Emer Suavinho ; Hyslop, Stephen

Afiliação do(s) autor(es)

^[1] Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Biochemical Pharmacology; v. 68, n. 2, p. 205-214, July 2004.
• Área do conhecimento: Ciências Biológicas - Farmacologia
• Assunto(s): Farmacologia molecular Fator natriurético atrial Inibidores da angiogênese Angiotensina II Peptídeo natriurético encefálico Óxido nítrico

Resumo

The chronic treatment of rats with N-omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) biosynthesis, results in hypertension. This inhibition of NO production results in activation of the renin-angiotensin system, with increased activity of the carboxypeptidase angiotensin I-converting enzyme (ACE). Since chronic NO inhibition increases ACE activity, we hypothesized that this inhibition could also affect the activities of other peptidases involved in cardiovascular functions. To test this possibility, we examined the activities of aminopeptidase M (APM), dipeptidyl peptidase IV (DPP IV), metalloendopeptidase 24.15 (MEP 24.15) and neutral endopeptidase 24.11 (NEP 24.11) in rat brain, heart, kidney, liver, lung and thoracic aorta. Male Wistar rats were treated chronically with L-NAME (80 mg kg(-1) per day) administered in the drinking water for 4 weeks and their organs then removed and processed for the determination of peptidase activities. Treatment with L-NAME did not significantly alter the activities of the four peptidases in brain, heart, kidney, liver and lung. In contrast, in aorta, the activity of APM was slightly but significantly reduced whereas those of DPP IV and MEP 24.15 were markedly enhanced; NEP 24.11 was not detected in this tissue. Immunoblotting for DPP IV and MEP 24.15 showed increased expression in aortic tissue. Neither L-NAME (1-100 muM) nor the NO donors sodium nitroprusside and 3-morpholinosydnonimine (SIN-1; 1-100 muM) had any consistent effect on the activity of recombinant MEP 24.15 or renal DPP IV. The importance of MEP 24.15 in peptide metabolism was continued in pentobartibal-anesthetized rats pretreated with the MEP 24.15 inhibitor N-[1-(R,S)carboxy-3-phenylpropyl]-Ala-Aib-Tyr-p-aminobenzoate (JA2), which significantly potentiated the hypotensive response to bradykinin. The altered peptidase activities seen in aorta may contribute to modulating vascular responses in this model of hypertension. (AU)

• Processo FAPESP: 00/01419-5 - Atividade e expressao de peptidases em ratos tratados cronicamente com l-name, um inibidor da biossintese de oxido nitrico.
• Beneficiário: ALESSANDRA LINARDI
• Modalidade de apoio: Bolsas no Brasil - Doutorado