title: Lack of potentiation of bradykinin by angiotensin-(1-7) in a type 2 diabetes model: role of insulin.
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 interaction between angiotensin-(1-7) (Ang-(1-7)) and bradykinin (BK), important components of these systems in an insulin resistance model of diabetes, and the effect of insulin on it. For this the response of mesenteric arterioles of anesthetized neonatal streptozotocin-induced (n-STZ) diabetic and control rats was evaluated using intravital microscopy. Though capable of potentiating BK in non-diabetic rats, Ang-(1-7) did not potentiate BK in n-STZ rats. Chronic but not acute insulin treatment restored the potentiation. This restorative effect of insulin was abolished by a K+ channel blocker (tetraethylammonium), by nitric oxide synthase inhibitor (N-nitro-L-arginine methyl ester) and by a cyclooxygenase inhibitor (indomethacin). On the other hand, Na(+)-,K(+)-ATPase inhibition (by ouabain) did not abolish the effect of insulin. There was no difference in mRNA and protein expression of B1 and B2 kinin receptor subtypes between n-STZ diabetic and control rats. Insulin treatment did not alter the kinin receptor expression. Our data allow us to conclude that diabetes impaired the interaction between BK and Ang-(1-7) and that insulin restores it. The restoring effect of insulin depends on membrane hyperpolarization, nitric oxide release and cyclooxygenease metabolites but not Na+K+-ATPase. Alteration of kinin receptor expression might not be involved in the restoring effect of insulin on the potentiation of BK by Ang-(1-7).
authors.affiliation: Department of Pharmacology, Institute of Biomedical Science, University of São Paulo. Av. Prof. Lineu Prestes, 1524, Cidade Universitária, 05508-900 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: D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018002:Receptors, Bradykinin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013311:Streptozocin / Q000633:toxicity; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010446:Peptide Fragments; D018002:Receptors, Bradykinin; D010042:Ouabain; D013311:Streptozocin; D019789:Tetraethylammonium; D000803:Angiotensin I; C118790:angiotensin I (1-7); D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin