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 (3 μM), thiorphan (3 μM), or vehicle a...
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2016-01-01
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Series: | Journal of Diabetes Research |
Online Access: | http://dx.doi.org/10.1155/2016/4846819 |
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author | P. P. Wołkow B. Bujak-Giżycka J. Jawień R. Olszanecki J. Madej J. Rutowski R. Korbut |
author_facet | P. P. Wołkow B. Bujak-Giżycka J. Jawień R. Olszanecki J. Madej J. Rutowski R. Korbut |
author_sort | P. P. Wołkow |
collection | DOAJ |
description | 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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id | doaj-art-617baa237af4493aaeee76937b64beb3 |
institution | Kabale University |
issn | 2314-6745 2314-6753 |
language | English |
publishDate | 2016-01-01 |
publisher | Wiley |
record_format | Article |
series | Journal of Diabetes Research |
spelling | doaj-art-617baa237af4493aaeee76937b64beb32025-02-03T01:10:02ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/48468194846819Exogenous Angiotensin I Metabolism in Aorta Isolated from Streptozotocin Treated Diabetic RatsP. P. Wołkow0B. Bujak-Giżycka1J. Jawień2R. Olszanecki3J. Madej4J. Rutowski5R. Korbut6Department of Pharmacology, Jagiellonian University Medical College, Krakow, PolandDepartment of Pharmacology, Jagiellonian University Medical College, Krakow, PolandDepartment of Pharmacology, Jagiellonian University Medical College, Krakow, PolandDepartment of Pharmacology, Jagiellonian University Medical College, Krakow, PolandDepartment of Pharmacology, Jagiellonian University Medical College, Krakow, PolandDepartment of Pharmacology, Medical Faculty, University of Rzeszów, Rzeszów, PolandDepartment of Pharmacology, Jagiellonian University Medical College, Krakow, PolandPurpose. 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.http://dx.doi.org/10.1155/2016/4846819 |
spellingShingle | P. P. Wołkow B. Bujak-Giżycka J. Jawień R. Olszanecki J. Madej J. Rutowski R. Korbut Exogenous Angiotensin I Metabolism in Aorta Isolated from Streptozotocin Treated Diabetic Rats Journal of Diabetes Research |
title | Exogenous Angiotensin I Metabolism in Aorta Isolated from Streptozotocin Treated Diabetic Rats |
title_full | Exogenous Angiotensin I Metabolism in Aorta Isolated from Streptozotocin Treated Diabetic Rats |
title_fullStr | Exogenous Angiotensin I Metabolism in Aorta Isolated from Streptozotocin Treated Diabetic Rats |
title_full_unstemmed | Exogenous Angiotensin I Metabolism in Aorta Isolated from Streptozotocin Treated Diabetic Rats |
title_short | Exogenous Angiotensin I Metabolism in Aorta Isolated from Streptozotocin Treated Diabetic Rats |
title_sort | exogenous angiotensin i metabolism in aorta isolated from streptozotocin treated diabetic rats |
url | http://dx.doi.org/10.1155/2016/4846819 |
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