Angiotensin-(1-7) and bradykinin interaction in diabetes mellitus: in vivo study.
The interaction between angiotensin-(1-7) (Ang-(1-7)) and bradykinin (BK) was determined in the mesentery of anesthetized Wistar alloxan-diabetic and non-diabetic rats using intravital microscopy. Impaired BK vasodilation observed in arterioles of diabetic rats was restored by acute and chronic insulin treatment as well as by enalapril. Though capable of potentiating BK in non-diabetic rats, Ang-(1-7) did not potentiate BK in diabetic rats. Chronic but not acute insulin treatment restored the potentiation, whereas enalapril did not. Potassium channel blockade (by tetraethylammonium (TEA)) but not nitric oxide (NO) synthase inhibition (by N-omega-nitro-L-arginine-methyl-esther (L-NAME)) abolished the restorative effect of insulin. Our data allow us to suggest that the alteration observed is restored by insulin by a mechanism involving membrane hyperpolarization but not NO release. The beneficial effect of enalapril in diabetes might not involve the potentiation of BK by Ang-(1-7).
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, Cidade Universitária, 05508-900 CEP, São Paulo, SP, Brazil.
Maria A
MA
Oliveira
Maria Helena C
MH
Carvalho
Dorothy
D
Nigro
Rita de Cássia A T
Rde C
Passaglia
Zuleica B
ZB
Fortes
D000803:Angiotensin I / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001920:Bradykinin / Q000378:metabolism* / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000378:metabolism*; D004656:Enalapril / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D004656:Enalapril; D000803:Angiotensin I; C118790:angiotensin I (1-7); D001920:Bradykinin