Androgen-induced hypertension in angiotensinogen deficient mice: Role of 20-HETE and EETS

Victor Garcia, Jennifer Cheng, Adam Weidenhammer, Yan Ding, Cheng Chia Wu, Fan Zhang, Katherine Gotlinger, J R Falck, Michal L. Schwartzman

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)124-130
Number of pages7
JournalProstaglandins and Other Lipid Mediators
Volume116-117
DOIs
StatePublished - Jan 1 2015

Fingerprint

Angiotensinogen
Dihydrotestosterone
Androgens
Hypertension
Lisinopril
Blood Vessels
Losartan
Blood pressure
Angiotensins
Renin-Angiotensin System
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Renin
20-hydroxyeicosa-6(Z),15(Z)-dienoic acid
Blood Pressure
Kidney

Keywords

  • 20-HETE
  • ACE
  • Androgen
  • Angiotensinogen
  • Hypertension

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

Cite this

Garcia, V., Cheng, J., Weidenhammer, A., Ding, Y., Wu, C. C., Zhang, F., ... Schwartzman, M. L. (2015). Androgen-induced hypertension in angiotensinogen deficient mice: Role of 20-HETE and EETS. Prostaglandins and Other Lipid Mediators, 116-117, 124-130. https://doi.org/10.1016/j.prostaglandins.2014.12.001

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 journalArticle

Garcia, V, Cheng, J, Weidenhammer, A, Ding, Y, Wu, CC, Zhang, F, Gotlinger, K, Falck, JR & Schwartzman, ML 2015, 'Androgen-induced hypertension in angiotensinogen deficient mice: Role of 20-HETE and EETS', Prostaglandins and Other Lipid Mediators, vol. 116-117, pp. 124-130. https://doi.org/10.1016/j.prostaglandins.2014.12.001
Garcia, Victor ; Cheng, Jennifer ; Weidenhammer, Adam ; Ding, Yan ; Wu, Cheng Chia ; Zhang, Fan ; Gotlinger, Katherine ; Falck, J R ; Schwartzman, Michal L. / Androgen-induced hypertension in angiotensinogen deficient mice : Role of 20-HETE and EETS. In: Prostaglandins and Other Lipid Mediators. 2015 ; Vol. 116-117. pp. 124-130.
@article{ac8d73c0dc2e4cc1b3da349e69b0b1ab,
title = "Androgen-induced hypertension in angiotensinogen deficient mice: Role of 20-HETE and EETS",
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.",
keywords = "20-HETE, ACE, Androgen, Angiotensinogen, Hypertension",
author = "Victor Garcia and Jennifer Cheng and Adam Weidenhammer and Yan Ding and Wu, {Cheng Chia} and Fan Zhang and Katherine Gotlinger and Falck, {J R} and Schwartzman, {Michal L.}",
year = "2015",
month = "1",
day = "1",
doi = "10.1016/j.prostaglandins.2014.12.001",
language = "English (US)",
volume = "116-117",
pages = "124--130",
journal = "Prostaglandins and Other Lipid Mediators",
issn = "1098-8823",
publisher = "Elsevier BV",

}

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 -