Abstract

application) The overall hypothesis to be tested in this proposal is that increases in production of lipoxygenase metabolites and decreases in production of epoxygenase metabolites contribute to enhanced vascular tone of preglomerular vessels and elevation in blood pressure associated with increased circulating levels of angiotensin II. Rats will be prepared with chronic infusion of angiotensin II and the development of hypertension followed. At selected time intervals, the metabolites of epoxygenase and lipoxygenase will be measured. The reactivity of renal microvasculatures will be evaluated and assayed for the production of the various metabolites of arachidonic acid. In addition, in vitro juxtamedullary nephron techniques combined with video microscopy will be used to determine preglomerular vascular tone in vitro; the various contributions of metabolites lipoxygenase and epoxygenase will be assessed using pharmacological inhibition of these probes both in the acute and chronic situation. Results of these studies will further define the renin-angiotensin system and determine the role of arachidonic acid metabolism in the development of angiotensin-dependent hypertension.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL059699-03
Application #
6139280
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1998-01-01
Project End
2001-12-31
Budget Start
2000-02-18
Budget End
2000-12-31
Support Year
3
Fiscal Year
2000
Total Cost
$92,972
Indirect Cost

  Institution

Name
Tulane University
Department
Physiology
Type
Schools of Medicine
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118

  Publications

Deng, Bing-Qing; Luo, Ying; Kang, Xin et al. (2017) Epoxide metabolites of arachidonate and docosahexaenoate function conversely in acute kidney injury involved in GSK3? signaling. Proc Natl Acad Sci U S A 114:12608-12613
Hwang, Sung Hee; Wagner, Karen; Xu, Jian et al. (2017) Chemical synthesis and biological evaluation of ?-hydroxy polyunsaturated fatty acids. Bioorg Med Chem Lett 27:620-625
Liu, Jun-Yan; Morisseau, Christophe; Huang, Huazhang et al. (2016) Screening of soluble epoxide hydrolase inhibitory ingredients from traditional Chinese medicines for anti-inflammatory use. J Ethnopharmacol 194:475-482
Imig, J D (2016) Epoxyeicosatrienoic Acids and 20-Hydroxyeicosatetraenoic Acid on Endothelial and Vascular Function. Adv Pharmacol 77:105-41
Liu, Jun-Yan; Tsai, Hsing-Ju; Morisseau, Christophe et al. (2015) In vitro and in vivo metabolism of N-adamantyl substituted urea-based soluble epoxide hydrolase inhibitors. Biochem Pharmacol 98:718-31
Wecksler, Aaron T; Hwang, Sung Hee; Liu, Jun-Yan et al. (2015) Biological evaluation of a novel sorafenib analogue, t-CUPM. Cancer Chemother Pharmacol 75:161-71
Walkowska, A; Kuczeriszka, M; Sadowski, J et al. (2015) High salt intake increases blood pressure in normal rats: putative role of 20-HETE and no evidence on changes in renal vascular reactivity. Kidney Blood Press Res 40:323-34
Bettaieb, Ahmed; Chahed, Samah; Tabet, George et al. (2014) Effects of soluble epoxide hydrolase deficiency on acute pancreatitis in mice. PLoS One 9:e113019
Wecksler, Aaron T; Hwang, Sung Hee; Wettersten, Hiromi I et al. (2014) Novel sorafenib-based structural analogues: in-vitro anticancer evaluation of t-MTUCB and t-AUCMB. Anticancer Drugs 25:433-46
Kujal, Petr; ?ertíková Chábová, Vera; Škaroupková, Petra et al. (2014) Inhibition of soluble epoxide hydrolase is renoprotective in 5/6 nephrectomized Ren-2 transgenic hypertensive rats. Clin Exp Pharmacol Physiol 41:227-37

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