Blood pressure-independent renoprotection in diabetic rats treated with AT1 receptor-neprilysin inhibition compared with AT1 receptor blockade alone

被引：37
作者：
Roksnoer, Lodi C. W. [1 ]
van Veghel, Richard [1 ]
Clahsen-van Groningen, Marian C. [3 ]
de Vries, Rene [1 ]
Garrelds, Ingrid M. [1 ]
Bhaggoe, Usha M. [1 ]
van Gool, Jeanette M. G. [1 ]
Friesema, Edith C. H. [1 ]
Leijten, Frank P. J. [1 ]
Hoorn, Ewout J. [2 ]
Danser, A. H. Jan [1 ]
Batenburg, Wendy W. [1 ]
机构：
[1] Erasmus MC, Div Pharmacol & Vasc Med, Dept Internal Med, Wytemaweg 80, NL-3015 CN Rotterdam, Netherlands
[2] Erasmus MC, Div Nephrol & Transplantat, Dept Internal Med, Wytemaweg 80, NL-3015 CN Rotterdam, Netherlands
[3] Erasmus MC, Dept Pathol, Wytemaweg 80, NL-3015 CN Rotterdam, Netherlands
来源：
CLINICAL SCIENCE | 2016年 / 130卷 / 14期
关键词：
AT(1) receptor antagonist; diabetes; hypertension; neprilysin inhibition; renin-angiotensin system; ATRIAL-NATRIURETIC-PEPTIDE; PRESERVED EJECTION FRACTION; ANGIOTENSIN-II; TRANSGENIC RATS; HEART-FAILURE; HYPERTENSIVE-RATS; DOUBLE-BLIND; RENIN GENE; PLASMA; MELLITUS;
D O I：
10.1042/CS20160197
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
ARNI [dual AT(1) (angiotensin II type 1) receptor-neprilysin inhibition] exerts beneficial effects on blood pressure and kidney function in heart failure, compared with ARB (AT(1) receptor blockade) alone. We hypothesized that ARNI improves cardiac and kidney parameters in diabetic TGR(mREN2) 27 rats, an angiotensin II-dependent hypertension model. Rats were made diabetic with streptozotocin for 5 or 12 weeks. In the final 3 weeks, rats were treated with vehicle, irbesartan (ARB) or irbesartan+thiorphan (ARNI). Blood pressure, measured by telemetry in the 5-week group, was lowered identically by ARB and ARNI. The heart weight/tibia length ratio in 12-week diabetic animals was lower after ARNI compared with after ARB. Proteinuria and albuminuria were observed from 8 weeks of diabetes onwards. ARNI reduced proteinuria more strongly than ARB, and a similar trend was seen for albuminuria. Kidneys of ARNI-treated animals showed less severe segmental glomerulosclerosis than those of ARB-treated animals. After 12 weeks, no differences between ARNI-and ARB-treated animals were found regarding diuresis, natriuresis, plasma endothelin-1, vascular reactivity (acetylcholine response) or kidney sodium transporters. Only ARNI-treated rats displayed endothelin type B receptor-mediated vasodilation. In conclusion, ARNI reduces proteinuria, glomerulosclerosis and heart weight in diabetic TGR(mREN2) 27 rats more strongly than does ARB, and this occurs independently of blood pressure.
引用
收藏
页码：1209 / 1220
页数：12
相关论文
共 39 条
  • [1] NO donors potentiate the β-adrenergic stimulation of ICa,L and the muscarinic activation of IK,ACh in rat cardiac myocytes
    Abi-Gerges, N
    Szabo, G
    Otero, AS
    Fischmeister, R
    Méry, PF
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 2002, 540 (02): : 411 - 424
  • [2] COMPARISON OF CANDOXATRIL AND ATRIAL-NATRIURETIC-FACTOR IN HEALTHY-MEN - EFFECTS ON HEMODYNAMICS, SYMPATHETIC ACTIVITY, HEART-RATE-VARIABILITY, AND ENDOTHELIN
    ANDO, S
    RAHMAN, MA
    BUTLER, GC
    SENN, BL
    FLORAS, JS
    [J]. HYPERTENSION, 1995, 26 (06) : 1160 - 1166
  • [3] Integrating drug pharmacokinetics for phenotyping individual renin response to angiotensin II blockade in humans
    Azizi, M
    Bissery, A
    Lamarre-Cliche, M
    Ménard, J
    [J]. HYPERTENSION, 2004, 43 (04) : 785 - 790
  • [4] TRANSGENIC RATS CARRYING THE MOUSE RENIN GENE - MORPHOLOGICAL CHARACTERIZATION OF A LOW-RENIN HYPERTENSION MODEL
    BACHMANN, S
    PETERS, J
    ENGLER, E
    GANTEN, D
    MULLINS, J
    [J]. KIDNEY INTERNATIONAL, 1992, 41 (01) : 24 - 36
  • [5] Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the γ-subunit
    Bruns, James B.
    Carattino, Marcelo D.
    Sheng, Shaohu
    Maarouf, Ahmad B.
    Weisz, Ora A.
    Pilewski, Joseph M.
    Hughey, Rebecca P.
    Kleyman, Thomas R.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (09) : 6153 - 6160
  • [6] Hyperfiltration and effect of nitric oxide inhibition on renal and endothelial function in humans with uncomplicated type 1 diabetes mellitus
    Cherney, David Z. I.
    Reich, Heather N.
    Jiang, Shan
    Har, Ronnie
    Nasrallah, Rania
    Hebert, Richard L.
    Lai, Vesta
    Scholey, James W.
    Sochett, Etienne B.
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY, INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2012, 303 (07) : R710 - R718
  • [7] CARDIAC RENIN AND ANGIOTENSINS - UPTAKE FROM PLASMA VERSUS IN-SITU SYNTHESIS
    DANSER, AHJ
    VANKATS, JP
    ADMIRAAL, PJJ
    DERKS, FHM
    LAMERS, JMJ
    VERDOUW, PD
    SAXENA, PR
    SCHALEKAMP, MADH
    [J]. HYPERTENSION, 1994, 24 (01) : 37 - 48
  • [8] Treatment of streptozotocin-induced diabetic rats with AVE7688, a vasopeptidase inhibitor - Effect on vascular and neural disease
    Davidson, Eric P.
    Kleinschmidt, Travis L.
    Oltman, Christine L.
    Lund, Donald D.
    Yorek, Mark A.
    [J]. DIABETES, 2007, 56 (02) : 355 - 362
  • [9] Renin-angiotensin system components in the interstitial fluid of the isolated perfused rat heart - Local production of angiotensin I
    deLannoy, LM
    Danser, AHJ
    vanKats, JP
    Schoemaker, RG
    Saxena, PR
    Schalekamp, MADH
    [J]. HYPERTENSION, 1997, 29 (06) : 1240 - 1251
  • [10] Regulatory binding partners and complexes of NHE3
    Donowitz, Mark
    Li, Xuhang
    [J]. PHYSIOLOGICAL REVIEWS, 2007, 87 (03) : 825 - 872
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