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The effect of insulin and enalapril on the potentiation of bradykinin-induced vasodilation by angiotensin-(1–7) in diabetes mellitus

Objective

In control normoglycemic rats, angiotensin-(1–7) [Ang-(1–7)] potentiates the bradykinin (BK)-induced vasodilation. We studied the effects of insulin and enalapril in the Ang-(1–7) and BK interaction in diabetes mellitus.

Design and methods

After 30 days of alloxan (40 mg/kg, intravenously), arteriolar reactivity was determined in vivo by intravital microscopy in anesthetized diabetic rats. The increase in arteriolar diameter (%) was measured before and after topical application of BK (1 pmol) and of Ang-(1–7) (100 pmol) + BK. Animals were treated acutely (4 IU, 4 hours before) or chronically (2 IU, 12 days) with insulin. The effect of enalapril (10 mg/kg per 21 days) and tetraethylammonium (90 pmol, topically), a potassium channel blocker, was also tested.

Results

In diabetic rats, topical application of BK induced a small vasodilation (2.5 ± 0.8%), which was augmented by acute insulin (5.6 ± 0.8%, P < 0.05), chronic insulin (4.3 ± 0.2%, P < 0.05) and enalapril (5.3 ± 0.3%, P < 0.05) treatments. The Ang-(1–7) + BK association did not modify the BK-induced vasodilation in diabetic rats (2.5 ± 0.8 vs 3.4 ± 1.0%), in rats acutely treated with insulin (5.6 ± 0.8% vs 6.0 ± 0.8%) and in enalapril-treated animals (5.3 ± 0.3% vs 6.2 ± 0.2%). However, in animals with chronic insulin treatment, BK responses were potentiated by Ang-(1–7) (8.3 ± 0.5%, P < 0.05), and this potentiating effect was reversed in the presence of tetraethylammonium (5.5 ± 0.7%, P < 0.05).

Conclusion

These data may indicate that membrane hyperpolarization may contribute to the restoring effect of insulin on the potentiation of BK-induced vasodilation by Ang-(1–7) on diabetic microvessels.

Acknowledgements

Support by PRONEX and FAPESP.

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Oliveira, M., Carvalho, M., Nigro, D. et al. The effect of insulin and enalapril on the potentiation of bradykinin-induced vasodilation by angiotensin-(1–7) in diabetes mellitus. Crit Care 7, P128 (2003). https://doi.org/10.1186/cc2324

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Keywords

  • Angiotensin
  • Enalapril
  • Potassium Channel
  • Bradykinin
  • Topical Application