Abstract
20-HETE is a potent inducer of endothelial ACE in vitro and administration of lisinopril or losartan attenuates blood pressure in models of 20-HETE-dependent hypertension. The present study was undertaken to further define the relationship between 20-HETE and the renin-angiotensin system in hypertension using an angiotensinogen-deficient mouse (Agt+/-). Treatment of male AGT+/- with 5α-dihydrotestosterone (DHT) increased systolic BP from 102 ± 2 to 125 ± 3 mmHg; in comparison, the same treatment raised BP in wild type (WT) from 110 ± 2 to 138 ± 2 mmHg. DHT increased vascular 20-HETE levels in AGT+/- and WT from 1.5 ± 0.7 and 2.1 ± 0.6 to 13.0 ± 2.0 and 15.8 ± 4.0 ng/mg, respectively. Concurrent treatment with the 20-HETE antagonist, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE) prevented the increases in BP in both AGT+/- and WT mice. Administration of 20-HEDE at the peak of the DHT-induced BP increase (12 days) reduced BP to basal levels after 48 h. Interestingly, basal levels of renal microvascular EETs were higher in AGT+/- compared to WT (55.2 ± 9.7 vs 20.0 ± 4.1 ng/mg) and treatment of AGT+/- with DHT decreased the levels of EETs (28.4 ± 5.1 ng/mg). DHT-mediated changes in vascular EET level were not observed in WT mice. Vascular Cyp4a12 and ACE protein levels were increased in both AGT+/- and WT by 30-40% and decreased with concomitant administration of 20-HEDE. Lisinopril was as effective as 20-HEDE in preventing DHT-mediated increases in BP in both AGT+/- and WT mice. This study substantiates our previous findings that the RAS plays an important role in 20-HETE-mediated hypertension. It also proposes a novel interaction between 20-HETE and EETs.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 124-130 |
| Number of pages | 7 |
| Journal | Prostaglandins and Other Lipid Mediators |
| Volume | 116-117 |
| DOIs | |
| State | Published - Jan 1 2015 |
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Keywords
- 20-HETE
- ACE
- Androgen
- Angiotensinogen
- Hypertension
ASJC Scopus subject areas
- Biochemistry
- Physiology
- Pharmacology
- Cell Biology
Cite this
Androgen-induced hypertension in angiotensinogen deficient mice : Role of 20-HETE and EETS. / Garcia, Victor; Cheng, Jennifer; Weidenhammer, Adam; Ding, Yan; Wu, Cheng Chia; Zhang, Fan; Gotlinger, Katherine; Falck, J R; Schwartzman, Michal L.
In: Prostaglandins and Other Lipid Mediators, Vol. 116-117, 01.01.2015, p. 124-130.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Androgen-induced hypertension in angiotensinogen deficient mice
T2 - Role of 20-HETE and EETS
AU - Garcia, Victor
AU - Cheng, Jennifer
AU - Weidenhammer, Adam
AU - Ding, Yan
AU - Wu, Cheng Chia
AU - Zhang, Fan
AU - Gotlinger, Katherine
AU - Falck, J R
AU - Schwartzman, Michal L.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 20-HETE is a potent inducer of endothelial ACE in vitro and administration of lisinopril or losartan attenuates blood pressure in models of 20-HETE-dependent hypertension. The present study was undertaken to further define the relationship between 20-HETE and the renin-angiotensin system in hypertension using an angiotensinogen-deficient mouse (Agt+/-). Treatment of male AGT+/- with 5α-dihydrotestosterone (DHT) increased systolic BP from 102 ± 2 to 125 ± 3 mmHg; in comparison, the same treatment raised BP in wild type (WT) from 110 ± 2 to 138 ± 2 mmHg. DHT increased vascular 20-HETE levels in AGT+/- and WT from 1.5 ± 0.7 and 2.1 ± 0.6 to 13.0 ± 2.0 and 15.8 ± 4.0 ng/mg, respectively. Concurrent treatment with the 20-HETE antagonist, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE) prevented the increases in BP in both AGT+/- and WT mice. Administration of 20-HEDE at the peak of the DHT-induced BP increase (12 days) reduced BP to basal levels after 48 h. Interestingly, basal levels of renal microvascular EETs were higher in AGT+/- compared to WT (55.2 ± 9.7 vs 20.0 ± 4.1 ng/mg) and treatment of AGT+/- with DHT decreased the levels of EETs (28.4 ± 5.1 ng/mg). DHT-mediated changes in vascular EET level were not observed in WT mice. Vascular Cyp4a12 and ACE protein levels were increased in both AGT+/- and WT by 30-40% and decreased with concomitant administration of 20-HEDE. Lisinopril was as effective as 20-HEDE in preventing DHT-mediated increases in BP in both AGT+/- and WT mice. This study substantiates our previous findings that the RAS plays an important role in 20-HETE-mediated hypertension. It also proposes a novel interaction between 20-HETE and EETs.
AB - 20-HETE is a potent inducer of endothelial ACE in vitro and administration of lisinopril or losartan attenuates blood pressure in models of 20-HETE-dependent hypertension. The present study was undertaken to further define the relationship between 20-HETE and the renin-angiotensin system in hypertension using an angiotensinogen-deficient mouse (Agt+/-). Treatment of male AGT+/- with 5α-dihydrotestosterone (DHT) increased systolic BP from 102 ± 2 to 125 ± 3 mmHg; in comparison, the same treatment raised BP in wild type (WT) from 110 ± 2 to 138 ± 2 mmHg. DHT increased vascular 20-HETE levels in AGT+/- and WT from 1.5 ± 0.7 and 2.1 ± 0.6 to 13.0 ± 2.0 and 15.8 ± 4.0 ng/mg, respectively. Concurrent treatment with the 20-HETE antagonist, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE) prevented the increases in BP in both AGT+/- and WT mice. Administration of 20-HEDE at the peak of the DHT-induced BP increase (12 days) reduced BP to basal levels after 48 h. Interestingly, basal levels of renal microvascular EETs were higher in AGT+/- compared to WT (55.2 ± 9.7 vs 20.0 ± 4.1 ng/mg) and treatment of AGT+/- with DHT decreased the levels of EETs (28.4 ± 5.1 ng/mg). DHT-mediated changes in vascular EET level were not observed in WT mice. Vascular Cyp4a12 and ACE protein levels were increased in both AGT+/- and WT by 30-40% and decreased with concomitant administration of 20-HEDE. Lisinopril was as effective as 20-HEDE in preventing DHT-mediated increases in BP in both AGT+/- and WT mice. This study substantiates our previous findings that the RAS plays an important role in 20-HETE-mediated hypertension. It also proposes a novel interaction between 20-HETE and EETs.
KW - 20-HETE
KW - ACE
KW - Androgen
KW - Angiotensinogen
KW - Hypertension
UR - http://www.scopus.com/inward/record.url?scp=84939945467&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84939945467&partnerID=8YFLogxK
U2 - 10.1016/j.prostaglandins.2014.12.001
DO - 10.1016/j.prostaglandins.2014.12.001
M3 - Article
C2 - 25526688
AN - SCOPUS:84939945467
VL - 116-117
SP - 124
EP - 130
JO - Prostaglandins and Other Lipid Mediators
JF - Prostaglandins and Other Lipid Mediators
SN - 1098-8823
ER -