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Vascular Endothelial ACE Deletion does not Prevent 20‐HETE‐dependent Vascular Remodeling
Author(s) -
Shkolnik Brian,
Garcia Victor,
Bernstein Kenneth,
Falck John,
Schwartzman Michal
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.630.4
Subject(s) - medicine , endocrinology , blood pressure , losartan , microvessel , antagonist , receptor , angiotensin ii , chemistry , angiogenesis
In vivo, 20‐HETE‐mediated hypertension in rodents is associated with increased vascular ACE expression and circulating Ang II levels. Administration of an ACE inhibitor or Ang II receptor blocker attenuates 20‐HETE‐mediated increases in blood pressure. ACE3/3 mice lack vascular endothelial ACE, exhibit attenuated ACE expression in the kidneys and display normal ACE and circulating Ang II levels in the plasma. Administration of a 21 day release pellet of 5α‐dihydrotestosterone (DHT), a known inducer of 20‐HETE production, increased systolic blood pressure significantly in age‐matched wild type (WT) mice (148±4 vs 99±2 mmHg) as compared to ACE3/3 mice (125±1 vs 99±1 mmHg) on day 14 and was maintained till day 21. DHT treatment increased preglomerular microvessel (PGMV) remodeling in both WT and ACE3/3 mice; however, remodeling was attenuated in the ACE3/3 mice (media thickness, 15.83±1.11 vs 9.80±0.56 μm) as opposed to the WT mice (22.17±0.92 vs 9.68±0.76 μm). Concurrent treatment with DHT and 20‐HEDGE, a 20‐HETE antagonist, prevented the increase in blood pressure as well as the changes in vascular remodeling in WT and ACE3/3 mice. Mice treated with DHT and losartan have a normalized blood pressure throughout the 21 days yet microvascular remodeling was not prevented in WT and ACE3/3 mice (media thickness, 14.75±0.75 vs 15.30±1.21 μm, respectively). These results suggest that vascular endothelial ACE/AngII contribute, in part, to 20‐HETE‐mediated microvascular remodeling in hypertension and that 20‐HETE have effects on microvascular remodeling independent of its action on ACE/AngII in the vascular endothelium.