ACE and non-ACE pathways in the renal vascular response to RAS interruption in type 1 diabetes mellitus
BACKGROUND: The enormous contribution of renin-angiotensin system (RAS) interruption with ACE (angiotensin-converting enzyme) inhibitors and angiotensin II receptor blockers (ARB) in the treatment of diabetic nephropathy has led to interest in the factors involved in angiotensin II (Ang II) generation. In normal subjects, RAS interruption using an ARB produced a 50% greater renal plasma flow (RPF) rise than with an ACE inhibitor, suggesting a substantial contribution of non-ACE pathways. Moreover, immunohistochemistry studies in kidneys of overtly proteinuric diabetic subjects showed up-regulation of chymase, an alternative Ang II-generating enzyme. Our aim was to determine the degree to which the non-ACE pathways contribute to RAS activation in type 1 diabetes mellitus (DM).
METHODS: Type 1 DM patients (N= 37, 14 M/23 F; age 31 +/- 2 years; DM duration 16 +/- 1.7 years; HbA1c 7.7.0 +/- 0.3%) were studied on a high-salt diet. They received captopril 25 mg po one day and candesartan 16 mg po the next day. RPF and glomerular filtration rate (GFR) were measured before and up to 4 hours after drug administration.
RESULTS: Both captopril and candesartan induced a significant rise in RPF (baseline vs. peak <0.0001 for both), and the rise was concordant for the 2 drugs (r= 0.77, P < 0.001). However, the RPF responses were not significantly different between the 2 drugs (captopril 72 +/- 11 mL/min/1.73 m(2), candesartan 75 +/- 12, P= 0.841).
CONCLUSION: In predominantly normoalbuminuric, normotensive type 1 DM, activation of the intrarenal RAS reflects a mechanism involving primarily the classic ACE pathway.
Medienart: |
Artikel |
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Erscheinungsjahr: |
2005 |
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Erschienen: |
2005 |
Enthalten in: |
Zur Gesamtaufnahme - volume:67 |
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Enthalten in: |
Kidney international - 67(2005), 3 vom: 15. März, Seite 1033-7 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Lansang, M Cecilia [VerfasserIn] |
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Anmerkungen: |
Date Completed 30.06.2005 Date Revised 03.12.2021 published: Print Citation Status MEDLINE |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM153562153 |
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100 | 1 | |a Lansang, M Cecilia |e verfasserin |4 aut | |
245 | 1 | 0 | |a ACE and non-ACE pathways in the renal vascular response to RAS interruption in type 1 diabetes mellitus |
264 | 1 | |c 2005 | |
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500 | |a Date Completed 30.06.2005 | ||
500 | |a Date Revised 03.12.2021 | ||
500 | |a published: Print | ||
500 | |a Citation Status MEDLINE | ||
520 | |a BACKGROUND: The enormous contribution of renin-angiotensin system (RAS) interruption with ACE (angiotensin-converting enzyme) inhibitors and angiotensin II receptor blockers (ARB) in the treatment of diabetic nephropathy has led to interest in the factors involved in angiotensin II (Ang II) generation. In normal subjects, RAS interruption using an ARB produced a 50% greater renal plasma flow (RPF) rise than with an ACE inhibitor, suggesting a substantial contribution of non-ACE pathways. Moreover, immunohistochemistry studies in kidneys of overtly proteinuric diabetic subjects showed up-regulation of chymase, an alternative Ang II-generating enzyme. Our aim was to determine the degree to which the non-ACE pathways contribute to RAS activation in type 1 diabetes mellitus (DM) | ||
520 | |a METHODS: Type 1 DM patients (N= 37, 14 M/23 F; age 31 +/- 2 years; DM duration 16 +/- 1.7 years; HbA1c 7.7.0 +/- 0.3%) were studied on a high-salt diet. They received captopril 25 mg po one day and candesartan 16 mg po the next day. RPF and glomerular filtration rate (GFR) were measured before and up to 4 hours after drug administration | ||
520 | |a RESULTS: Both captopril and candesartan induced a significant rise in RPF (baseline vs. peak <0.0001 for both), and the rise was concordant for the 2 drugs (r= 0.77, P < 0.001). However, the RPF responses were not significantly different between the 2 drugs (captopril 72 +/- 11 mL/min/1.73 m(2), candesartan 75 +/- 12, P= 0.841) | ||
520 | |a CONCLUSION: In predominantly normoalbuminuric, normotensive type 1 DM, activation of the intrarenal RAS reflects a mechanism involving primarily the classic ACE pathway | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
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650 | 7 | |a Biphenyl Compounds |2 NLM | |
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700 | 1 | |a Stevanovic, Radomir |e verfasserin |4 aut | |
700 | 1 | |a Price, Deborah A |e verfasserin |4 aut | |
700 | 1 | |a Laffel, Lori M B |e verfasserin |4 aut | |
700 | 1 | |a Hollenberg, Norman K |e verfasserin |4 aut | |
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