A therapeutic approach to treat cardiovascular dysfunction of diabetes.
Exp Toxicol Pathol
; 64(7-8): 847-53, 2012 Nov.
Article
em En
| MEDLINE
| ID: mdl-21474293
ABSTRACT
Diabetes greatly increases risk of cardiovascular dysfunction and interruptions of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) have been shown to reduce the risk by alteration in extracellular matrix. We hypothesized that minocycline induced MMP-2 and MMP-9 inhibition can be enhanced by aspirin (through its COX and tPA inhibitory action) and this combination can reduce cardiovascular dysfunction of diabetes. Four weeks after diabetes induction (streptozotocin, 55 mg/kg, i.p.), rats were treated with minocycline (50 mg/kg, p.o.), aspirin (50 mg/kg, p.o.), or minocycline (50 mg/kg, p.o.) plus aspirin (50 mg/kg, p.o.) for a period of next four weeks. At the end of eighth week arterial pressure, heart rate and left ventricular pressure were recorded. Contractile response to phenylephrine (10(-5) M) and relaxation responses to acetylcholine (10(-9)-10(-4) M) were obtained from aortic rings of diabetic rats. Gel zymography was performed to evaluate MMP-2 and MMP-9 levels. Heart rate, mean arterial pressure, dp/dt(max) and dp/dt(min) were found significantly decreased in STZ diabetic rats when compared with normoglycemic group. Treatment with combination of minocycline and aspirin significantly ameliorate these compared to vehicle treated diabetic group. Endothelium-dependent relaxation responses induced by acetylcholine were decreased in diabetic rats and significantly higher in combination treated group. Collagen, MMP-2 and MMP-9 levels were significantly decreased in combined treated group when compared with diabetic control. Present study revealed that aspirin potentate minocycline induced MMP-2 and MMP-9 inhibition to ameliorate cardiovascular dysfunction of diabetes and this combination can be an approach for the treatment.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Aspirina
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Diabetes Mellitus Experimental
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Cardiomiopatias Diabéticas
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Inibidores de Metaloproteinases de Matriz
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Minociclina
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article