title: Enalapril treatment corrects the reduced response to bradykinin in diabetes increasing the B2 protein expression.
abstract: Considering the growing importance of the interaction between components of kallikrein-kinin and renin-angiotensin systems in physiological and pathological processes, particularly in diabetes mellitus, the aim of the present study was to investigate the effect of enalapril on the reduced response of bradykinin and on the interaction between angiotensin-(1-7) (Ang-(1-7)) and bradykinin (BK), important components of these systems, in an insulin-resistance model of diabetes. For the above purpose, the response of mesenteric arterioles of anesthetized neonatal streptozotocin-induced (n-STZ) diabetic and control rats was evaluated using intravital microscopy. In n-STZ diabetic rats, enalapril treatment restored the reduced response to BK but not the potentiation of BK by Ang-(1-7) present in non-diabetic rats. The restorative effect of enalapril was observed at a dose that did not correct the altered parameters induced by diabetes such as hyperglycemia, glicosuria, insulin resistance but did reduce the high blood pressure levels of n-SZT diabetic rats. There was no difference in mRNA and protein expressions of B1 and B2 kinin receptor subtypes between n-STZ diabetic and control rats. Enalapril treatment increased the B2 kinin receptor expression. From our data, we conclude that in diabetes enalapril corrects the impaired BK response probably by increasing the expression of B2 receptors. The lack of potentiation of BK by Ang-(1-7) is not corrected by this agent.
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Cidade Universitária, São Paulo, Brazil.
authors.forename: Viviani Milan Ferreira
authors.initials: VM
authors.lastname: Rastelli
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: Oliveira
authors.forename: Rosangela
authors.initials: R
authors.lastname: dos Santos
authors.forename: Rita
authors.initials: R
authors.lastname: de Cássia Tostes Passaglia
authors.forename: Dorothy
authors.initials: D
authors.lastname: Nigro
authors.forename: Maria Helena Catelli
authors.initials: MH
authors.lastname: de Carvalho
authors.forename: Zuleica Bruno
authors.initials: ZB
authors.lastname: Fortes
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000959:Antihypertensive Agents / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004656:Enalapril / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1 / Q000235:genetics* / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000959:Antihypertensive Agents; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D004656:Enalapril; D001920:Bradykinin