Exogenous Angiotensin I Metabolism in Aorta Isolated from Streptozotocin Treated Diabetic Rats

Abstract EN

Purpose.

Products of angiotensin (ANG) I metabolism may predispose to vascular complications of diabetes mellitus.

Methods.

Diabetes was induced with streptozotocin (75 mg/kg i.p.).

Rat aorta fragments, isolated 4 weeks later, were pretreated with perindoprilat (3 μM), thiorphan (3 μM), or vehicle and incubated for 15 minutes with ANG I (1 μM).

Products of ANG I metabolism through classical (ANG II, ANG III, and ANG IV) and alternative (ANG (1–9), ANG (1–7), and ANG (1–5)) pathways were measured in the buffer, using liquid chromatography-mass spectrometry.

Results.

Incubation with ANG I resulted in higher concentration of ANG II (P = 0.02, vehicle pretreatment) and lower of ANG (1–9) ( P = 0.048 , perindoprilat pretreatment) in diabetes.

Preference for the classical pathway is suggested by higher ANG III/ANG (1–7) ratios in vehicle ( P = 0.03 ), perindoprilat ( P = 0.02 ), and thiorphan pretreated ( P = 0.02 ) diabetic rat.

Within the classical pathway, ratios of ANG IV/ANG II ( P = 0.01 ) and of ANG IV/ANG III ( P = 0.049 ), but not of ANG III/ANG II are lower in diabetes.

Conclusions.

Diabetes in rats led to preference toward deleterious (ANG II, ANG III) over protective (ANG IV, ANG (1–9), and ANG (1–7)) ANG I metabolites.