Exogenous Angiotensin I Metabolism in Aorta Isolated from Streptozotocin Treated Diabetic Rats.
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 (3μM), thiorphan (3μM), or vehicle and incubated for 15 minutes with ANG I (1μM). 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.
Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland; Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Krakow, Poland.
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0000-0002-9322-5545
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Wołkow
Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland; Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Krakow, Poland.
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Bujak-Giżycka
Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
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Jawień
Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
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Olszanecki
Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
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Madej
Department of Pharmacology, Medical Faculty, University of Rzeszów, Rzeszów, Poland.
J
J
Rutowski
Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
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Korbut
D000803:Angiotensin I / Q000187:drug effects / Q000378:metabolism*; D000804:Angiotensin II / Q000187:drug effects / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D002853:Chromatography, Liquid; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D013058:Mass Spectrometry; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015244:Thiorphan / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D010446:Peptide Fragments; D011480:Protease Inhibitors; D000804:Angiotensin II; C053500:perindoprilat; D000803:Angiotensin I; D015244:Thiorphan; C118790:angiotensin I (1-7)