Donate Help Contact The AHA Sign In Home
American Heart Association
Hypertension
Search: search_blue_button Advanced Search
« Previous Article | Table of Contents | Next Article »
Hypertension. 2007;50:123-129
Published online before print June 4, 2007, doi: 10.1161/HYPERTENSIONAHA.107.089599
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Data Supplement
Right arrow All Versions of this Article:
50/1/123    most recent
HYPERTENSIONAHA.107.089599v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Singh, H.
Right arrow Articles by Schwartzman, M. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Singh, H.
Right arrow Articles by Schwartzman, M. L.
Related Collections
Right arrow Other hypertension
Right arrow Endothelium/vascular type/nitric oxide
Right arrowRelated Article

(Hypertension. 2007;50:123.)
© 2007 American Heart Association, Inc.

Original Articles

Vascular Cytochrome P450 4A Expression and 20-Hydroxyeicosatetraenoic Acid Synthesis Contribute to Endothelial Dysfunction in Androgen-Induced Hypertension

Harpreet Singh; Jennifer Cheng; Huan Deng; Rowena Kemp; Tsuneo Ishizuka; Alberto Nasjletti; Michal Laniado Schwartzman

From the Department of Pharmacology, New York Medical College, Valhalla.

Correspondence to Michal Laniado Schwartzman, Department of Pharmacology, New York Medical College, Valhalla, NY 10595. E-mail michal_schwartzman{at}nymc.edu

Epidemiological evidence suggests a role for sex-dependent mechanisms in the pathophysiology of hypertension. It has been shown that 5{alpha}-dihydrotestosterone (DHT) administration (56 mg/kg of body weight per day IP for 14 days) increases blood pressure, cytochrome P450 4A expression, and 20-hydroxyeicosatetraenoic acid synthesis in rats. We examined whether increased vascular 20-hydroxyeicosatetraenoic acid synthesis underlies endothelial dysfunction and hypertension in DHT-treated male Sprague–Dawley rats by using HET0016, a selective cytochrome P450 4A inhibitor. Coadministration of HET0016 (10 mg/kg per day IP for 14 days) to DHT-treated rats markedly reduced DHT-induced interlobar arterial production of 20-hydroxyeicosatetraenoic acid (14.3±1.5 versus 1.5±0.5 ng/mg of protein per hour; P<0.05), superoxide anion (246±47 versus 31±8 cpm/µg of protein), and the levels of gp91-phox, p47-phox, and 3-nitrosylated proteins. Moreover, the maximal relaxing response to acetylcholine in phenylephrine-preconstricted renal interlobar arteries from DHT-treated rats (42.8±4.8%) significantly (P<0.05) increased in the presence of HET0016 (81.5±10.8%). Importantly, the administration of HET0016 negated DHT-induced hypertension; systolic blood pressure was reduced from 146±2 mm Hg in DHT-treated rats to 130±1 mm Hg (P<0.05). The results strongly implicate vascular cytochrome P450 4A–derived 20-hydroxyeicosatetraenoic acid in the development of androgen-induced endothelial dysfunction and hypertension.


Key Words: hypertension • endothelial dysfunction • cytochrome P450 • NO • superoxide anion • 20-HETE


Related Article:

Does 20-Hydroxyeicosatetraenoic Acid Contribute to Sex Differences in Cardiovascular Risk by Increasing Oxidative Stress?
Richard J. Roman and Julian H. Lombard
Hypertension 2007 50: 37-38. [Full Text] [PDF]



This article has been cited by other articles:


Home page
 HypertensionHome page
C. Fava, M. Montagnana, P. Almgren, L. Rosberg, G. Lippi, B. Hedblad, G. Engstrom, G. Berglund, P. Minuz, and O. Melander
The V433M Variant of the CYP4F2 Is Associated With Ischemic Stroke in Male Swedes Beyond Its Effect on Blood Pressure
Hypertension, August 1, 2008; 52(2): 373 - 380.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
P. Minuz, H. Jiang, C. Fava, L. Turolo, S. Tacconelli, M. Ricci, P. Patrignani, A. Morganti, A. Lechi, and J. C. McGiff
Altered Release of Cytochrome P450 Metabolites of Arachidonic Acid in Renovascular Disease
Hypertension, May 1, 2008; 51(5): 1379 - 1385.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
N. C. Ward, I-J. Tsai, A. Barden, F. M. van Bockxmeer, I. B. Puddey, J. M. Hodgson, and K. D. Croft
A Single Nucleotide Polymorphism in the CYP4F2 but not CYP4A11 Gene Is Associated With Increased 20-HETE Excretion and Blood Pressure
Hypertension, May 1, 2008; 51(5): 1393 - 1398.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. Cheng, J.-S. Ou, H. Singh, J. R. Falck, D. Narsimhaswamy, K. A. Pritchard Jr., and M. L. Schwartzman
20-Hydroxyeicosatetraenoic acid causes endothelial dysfunction via eNOS uncoupling
Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H1018 - H1026.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
T. Ishizuka, J. Cheng, H. Singh, M. D. Vitto, V. L. Manthati, J. R. Falck, and M. Laniado-Schwartzman
20-Hydroxyeicosatetraenoic Acid Stimulates Nuclear Factor-{kappa}B Activation and the Production of Inflammatory Cytokines in Human Endothelial Cells
J. Pharmacol. Exp. Ther., January 1, 2008; 324(1): 103 - 110.
[Abstract] [Full Text] [PDF]


Hypertension Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 2007 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.