Key result
Streptozotocin-induced diabetes in rats shifted angiotensin I metabolism in isolated aorta toward deleterious metabolites like ANG II (P=0.02) and away from protective metabolites.
In a diabetic rat model, aortic metabolism of angiotensin I shifts toward the classical pathway, producing more deleterious metabolites like ANG II and ANG III.
Should not yet alter diabetes vascular management; hypothesis-generating for angiotensin pathway roles in complications.
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.
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Wołkow et al. (2016) studied Diabetes mellitus. Streptozotocin-induced diabetes vs. Non-diabetic rats was evaluated on Concentration of ANG II after incubation with ANG I (vehicle pretreatment) (p=0.02). Streptozotocin-induced diabetes in rats shifted angiotensin I metabolism in isolated aorta toward deleterious metabolites like ANG II (P=0.02) and away from protective metabolites.
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