Enalapril treatment corrects the reduced response to bradykinin in diabetes increasing the B2 protein expression.
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.
Rastelli
Viviani Milan Ferreira
VM
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Cidade Universitária, São Paulo, Brazil.
Oliveira
Maria Aparecida
MA
dos Santos
Rosangela
R
de Cássia Tostes Passaglia
Rita
R
Nigro
Dorothy
D
de Carvalho
Maria Helena Catelli
MH
Fortes
Zuleica Bruno
ZB
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
D000959:Antihypertensive Agents; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D004656:Enalapril; D001920:Bradykinin