Inhibition of epoxyeicosatrienoic acid production in rats with cirrhosis has beneficial effects on portal hypertension by reducing splanchnic vasodilation

Hepatology ◽  
2016 ◽  
Vol 64 (3) ◽  
pp. 923-930 ◽  
Author(s):  
Marco Di Pascoli ◽  
Francesca Zampieri ◽  
Alberto Verardo ◽  
Paola Pesce ◽  
Cristian Turato ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Acid Production ◽  
Epoxyeicosatrienoic Acid ◽  
Beneficial Effects ◽  
Splanchnic Vasodilation

Inhibition of Eets Production in Cirrhotic Rats has Beneficial Effects on Portal Hypertension by Reducing Splanchnic Vasodilation

2016 ◽  
Vol 64 (2) ◽  
pp. S449
Author(s):  
M. Di Pascoli ◽  
F. Zampieri ◽  
A. Verardo ◽  
P. Angeli ◽  
D. Sacerdoti ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Beneficial Effects ◽  
Splanchnic Vasodilation

Beneficial effects of combined terlipressin and tetramethylpyrazine administration on portal hypertensive rats

1999 ◽  
Vol 77 (8) ◽  
pp. 618-624 ◽  
Author(s):  
Fang-Chi Chang ◽  
Yi-Tsau Huang ◽  
Han-Chieh Lin ◽  
Chuang-Ye Hong ◽  
Jaung-Geng Lin ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Venous Pressure ◽  
Peripheral Resistance ◽  
Therapeutic Effects ◽  
Portal Vein Ligation ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Beneficial Effects ◽  
Sprague Dawley Rats ◽  
Duct Ligation

The purpose of this study was to investigate the therapeutic effects of terlipressin (TP) alone or in combination with tetramethylpyrazine (TMP) on anesthetized portal hypertensive rats. Portal hypertension was induced by either partial portal vein ligation (PVL, without cirrhosis) or bile duct ligation (BDL, with cirrhosis) in Sprague-Dawley rats. Each PVL or BDL rat received only one of the two regimens: vehicle for 3 min followed by TP (0.017 mg·kg-1·min-1 for 3 min) or TMP (10 mg·kg-1·min-1 for 3 min) followed by TP. In PVL rats, infusion of vehicle followed by TP induced significant reduction of portal venous pressure (PVP, -15.0 ± 1.0%) and prominent elevation of mean arterial pressure (MAP, 57.3 ± 8.1%) as well as total peripheral resistance (TPR, 113 ± 11%) from baseline, and there was a cardiodepressant response (cardiac index, CI, -26.3 ± 1.1%). Infusion of TMP followed by TP induced significant reduction of PVP (-20.3 ± 0.4%) and CI (-9.9 ± 1.2%) and significant elevation of MAP (31.3 ± 2.5%) and TPR (46.0 ± 4.1%) from baseline. In BDL rats, infusion of vehicle followed by TP also induced significant reduction of PVP (-13.8 ± 1.7%) but an increase in MAP (57.1 ± 2.2%) and TPR (101 ± 6%) from baseline, and there also was a cardiodepressant response (CI, -21.4 ± 2.3%). Infusion of TMP followed by TP induced significant reduction of PVP (-18.9 ± 1.4%) and CI (-11.9 ± 2.1%), but an increase in MAP (36.2 ± 2.5%) and TPR (55.0 ± 5.2%). Compared with vehicle followed by TP, TMP not only significantly enhanced portal hypotensive (PVP reduction) effects of TP but also attenuated the systemic pressor (MAP and TPR elevation) and cardiodepressant (CI reduction) effects of TP in both PVL and BDL rats. Our results suggest that TP, alone or in combination with TMP, induced portal hypotensive effects in two models of portal hypertensive rats. Combination of TP and TMP was beneficial in enhancing portal hypotensive effects of TP and ameliorating the systemic pressor and cardiodepressant effects of TP.Key words: terlipressin, tetramethylpyrazine, cirrhosis, portal hypertension, hemodynamics.

Atrophy of mesenteric sympathetic innervation may contribute to splanchnic vasodilation in rat portal hypertension

2010 ◽  
Vol 30 (4) ◽  
pp. 593-602 ◽  
Author(s):  
Mar Coll ◽  
María Martell ◽  
Imma Raurell ◽  
Nahia Ezkurdia ◽  
Silvia Cuenca ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Sympathetic Innervation ◽  
Splanchnic Vasodilation

scholarly journals The Cytochrome P450 Slow Metabolizers CYP2C9*2 and CYP2C9*3 Directly Regulate Tumorigenesis via Reduced Epoxyeicosatrienoic Acid Production

2018 ◽  
Vol 78 (17) ◽  
pp. 4865-4877 ◽  
Author(s):  
Lindsay N. Sausville ◽  
Mahesha H. Gangadhariah ◽  
Manuel Chiusa ◽  
Shaojun Mei ◽  
Shouzuo Wei ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Acid Production ◽  
Epoxyeicosatrienoic Acid ◽  
Slow Metabolizers

scholarly journals EET intervention on Wnt1, NOV, and HO-1 signaling prevents obesity-induced cardiomyopathy in obese mice

2017 ◽  
Vol 313 (2) ◽  
pp. H368-H380 ◽  
Author(s):  
Jian Cao ◽  
Shailendra P. Singh ◽  
John A. McClung ◽  
Gregory Joseph ◽  
Luca Vanella ◽  
...  
Keyword(s):  
Heart Failure ◽  
Vascular Function ◽  
Fasting Blood Glucose ◽  
Peroxisome Proliferator ◽  
Epoxyeicosatrienoic Acid ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cardiac Tissues ◽  
Beneficial Effects ◽  
Signaling Mechanisms ◽  
Mitochondrial Integrity

We have previously reported that epoxyeicosatrienoic acid (EET) has multiple beneficial effects on vascular function; in addition to its antiapoptotic action, it increases insulin sensitivity and inhibits inflammation. To uncover the signaling mechanisms by which EET reduces cardiomyopathy, we hypothesized that EET infusion might ameliorate obesity-induced cardiomyopathy by improving heme oxygenase (HO)-1, Wnt1, thermogenic gene levels, and mitochondrial integrity in cardiac tissues and improved pericardial fat phenotype. EET reduced levels of fasting blood glucose and proinflammatory adipokines, including nephroblastoma overexpressed (NOV) signaling, while increasing echocardiographic fractional shortening and O2 consumption. Of interest, we also noted a marked improvement in mitochondrial integrity, thermogenic genes, and Wnt 1 and HO-1 signaling mechanisms. Knockout of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in EET-treated mice resulted in a reversal of these beneficial effects including a decrease in myocardial Wnt1 and HO-1 expression and an increase in NOV. To further elucidate the effects of EET on pericardial adipose tissues, we observed EET treatment increases in adiponectin, PGC-1α, phospho-AMP-activated protein kinase, insulin receptor phosphorylation, and thermogenic genes, resulting in a “browning” pericardial adipose phenotype under high-fat diets. Collectively, these experiments demonstrate that an EET agonist increased Wnt1 and HO-1 signaling while decreasing NOV pathways and the progression of cardiomyopathy. Furthermore, this report presents a portal into potential therapeutic approaches for the treatment of heart failure and metabolic syndrome. NEW & NOTEWORTHY The mechanism by which EET acts on obesity-induced cardiomyopathy is unknown. Here, we describe a previously unrecognized function of EET infusion that inhibits nephroblastoma overexpressed (NOV) levels and activates Wnt1, hence identifying NOV inhibition and enhanced Wnt1 expression as novel pharmacological targets for the prevention and treatment of cardiomyopathy and heart failure. Listen to this article's corresponding podcast at http://ajpheart.physiology.org/content/early/2017/05/31/ajpheart.00093.2017 .

scholarly journals Beneficial Effects of Macroporous Resin Extract of Dendrobium candidum Leaves in Rats with Hyperuricemia Induced by a High-Purine Diet

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xiao-Jing Lou ◽  
Yu-Zhi Wang ◽  
Shan-Shan Lei ◽  
Xinglishang He ◽  
Ting-Ting Lu ◽  
...  
Keyword(s):  
Uric Acid ◽  
Acid Production ◽  
Biochemical Parameters ◽  
Water Extract ◽  
Macroporous Resin ◽  
Beneficial Effects ◽  
Liver And Kidney ◽  
Dendrobium Candidum ◽  
Resin Extract ◽  
Liver And Kidney Damage

Objectives. The incidence of hyperuricemia (HUA) is increasing year by year, and there are no ideal drugs for the treatment; the existing ones can cause serious liver and kidney damage. We have confirmed that the water extract of Dendrobium candidum leaves could reduce the level of uric acid in rats, but the active ingredients remain unknown, and the mechanism is not well understood. This research investigated the therapeutic effect of the macroporous resin extract of the Dendrobium candidum leaf (DLE) on hyperuricemia. In this study, hyperuricemia was induced in rats by a 5-week high-purine diet. After that, DLE was administered continuously for 9 weeks. The result showed that biochemical parameters of liver and kidney function, especially serum uric acid (UA) levels, were significantly improved with DLE, which may relate to the reduction of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the liver. Moreover, DLE could significantly prevent kidney and liver from damage, and intestinal injury and reduce inflammation in hyperuricemic rats by inhibiting the expression of both NF-κB and TLR4 proteins. These results showed that the macroporous resin extract of the Dendrobium candidum leaves may be effective for the treatment of hyperuricemia in rats by inhibiting uric acid production and decreasing inflammation.

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