scholarly journals Modulation of Arachidonic Acid Metabolism in the Rat Kidney by Sulforaphane: Implications for Regulation of Blood Pressure

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Fawzy Elbarbry ◽  
Anke Vermehren-Schmaedick ◽  
Agnieszka Balkowiec
Keyword(s):  
Blood Pressure ◽  
Drinking Water ◽  
Arachidonic Acid ◽  
Epoxide Hydrolase ◽  
Rat Kidney ◽  
Soluble Epoxide Hydrolase ◽  
Arachidonic Acid Metabolism ◽  
Dependent Manner ◽  
Shr Rats ◽  
Arterial Blood

Background. We investigated the effects of sulforaphane (SF), the main active isothiocyanate in cruciferous vegetables, on arachidonic acid (AA) metabolism in the kidney and its effect on arterial blood pressure, using spontaneously hypertensive rats (SHR) as models. Methods. Rats were treated for 8 weeks with either drinking water alone (control) or SF (20 or 40 mg/kg) added to drinking water. Mean arterial pressure (MAP) was measured at 7-day intervals throughout the study. At the end of treatment rats were euthanized, and kidneys were harvested to prepare microsomes and measure enzymes involved in regulation of vasoactive metabolites: CYP4A, the key enzyme in the formation of 20-hydroxyeicosatetraenoic acid, and the soluble epoxide hydrolase, which is responsible for the degradation of the vasodilator metabolites such as epoxyeicosatetraenoic acids. Effect of SF on kidney expression of CYP4A was investigated by immunoblotting. Results. We found that treatment with SF leads to significant reductions in both, the expression and activity of renal CYP4A isozymes, as well as the activity of soluble epoxide hydrolase (sEH). Consistent with these data, we have found that treatment with SF resisted the progressive rise in MAP in the developing SHR in a dose-dependent manner. Conclusion. This is the first demonstration that SF modulates the metabolism of AA by both P450 enzymes and sEH in SHR rats. This may represent a novel mechanism by which SF protects SHR rats against the progressive rise in blood pressure.

Acute arsenic toxicity alters cytochrome P450 and soluble epoxide hydrolase and their associated arachidonic acid metabolism in C57Bl/6 mouse heart

Xenobiotica ◽  
2012 ◽  
Vol 42 (12) ◽  
pp. 1235-1247 ◽  
Author(s):  
Anwar Anwar-Mohamed ◽  
Ahmed A. El-Sherbeni ◽  
Seok H. Kim ◽  
Hassan N. Althurwi ◽  
Beshay N. M. Zordoky ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Epoxide Hydrolase ◽  
Acid Metabolism ◽  
Soluble Epoxide Hydrolase ◽  
Arachidonic Acid Metabolism ◽  
Mouse Heart ◽  
Arsenic Toxicity

scholarly journals Inhibition of Soluble Epoxide Hydrolase Attenuates Bosutinib-Induced Blood Pressure Elevation

Hypertension ◽  
2021 ◽  
Author(s):  
Zhen Cui ◽  
Bochuan Li ◽  
Yanhong Zhang ◽  
Jinlong He ◽  
Xuelian Shi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Side Effects ◽  
Epoxide Hydrolase ◽  
Endothelial Activation ◽  
Soluble Epoxide Hydrolase ◽  
Mesenteric Arteries ◽  
Arterial Blood ◽  
Soluble Epoxide Hydrolase Inhibitor

Endothelial cells play a critical role in maintaining homeostasis of vascular function, and endothelial activation is involved in the initial step of atherogenesis. Previously, we reported that Abl kinase mediates shear stress–induced endothelial activation. Bosutinib, a dual inhibitor of Src and Abl kinases, exerts an atheroprotective effect; however, recent studies have demonstrated an increase in the incidence of side effects associated with bosutinib, including increased arterial blood pressure (BP). To understand the effects of bosutinib on BP regulation and the mechanistic basis for novel treatment strategies against vascular dysfunction, we generated a line of mice conditionally lacking c-Abl in endothelial cells (endothelial cell- Abl KO ). Knockout mice and their wild-type littermates ( Abl f/f ) were orally administered a clinical dose of bosutinib, and their BP was monitored. Bosutinib treatment increased BP in both endothelial cell- Abl KO and Abl f/f mice. Furthermore, acetylcholine-evoked endothelium-dependent relaxation of the mesenteric arteries was impaired by bosutinib treatment. RNA sequencing of mesenteric arteries revealed that the CYP (cytochrome P450)-dependent metabolic pathway was involved in regulating BP after bosutinib treatment. Additionally, bosutinib treatment led to an upregulation of soluble epoxide hydrolase in the arteries and a lower plasma content of eicosanoid metabolites in the CYP pathway in mice. Treatment with 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea, a soluble epoxide hydrolase inhibitor, reversed the bosutinib-induced changes to the eicosanoid metabolite profile, endothelium-dependent vasorelaxation, and BP. Thus, the present study demonstrates that upregulation of soluble epoxide hydrolase mediates bosutinib-induced elevation of BP, independent of c-Abl. The addition of soluble epoxide hydrolase inhibitor in patients treated with bosutinib may aid in preventing vascular side effects.

scholarly journals Soluble epoxide hydrolase gene deletion attenuates renal injury and inflammation with DOCA-salt hypertension

2009 ◽  
Vol 297 (3) ◽  
pp. F740-F748 ◽  
Author(s):  
Marlina Manhiani ◽  
Jeffrey E. Quigley ◽  
Sarah F. Knight ◽  
Shiva Tasoobshirazi ◽  
TarRhonda Moore ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Epoxide Hydrolase ◽  
Gene Deletion ◽  
Soluble Epoxide Hydrolase ◽  
Glomerular Injury ◽  
Renal Protection ◽  
Renal Inflammation ◽  
Arterial Blood ◽  
Salt Hypertension ◽  
Salt Sensitive Hypertension

Inhibition of soluble epoxide hydrolase (sEH) has been shown to be renal protective in rat models of salt-sensitive hypertension. Here, we hypothesize that targeted disruption of the sEH gene (Ephx2) prevents both renal inflammation and injury in deoxycorticosterone acetate plus high salt (DOCA-salt) hypertensive mice. Mean arterial blood pressure (MAP) increased significantly in the DOCA-salt groups, and MAP was lower in Ephx2−/− DOCA-salt (129 ± 3 mmHg) compared with wild-type (WT) DOCA-salt (145 ± 2 mmHg) mice. Following 21 days of treatment, WT DOCA-salt urinary MCP-1 excretion increased from control and was attenuated in the Ephx2−/− DOCA-salt group. Macrophage infiltration was reduced in Ephx2−/− DOCA-salt compared with WT DOCA-salt mice. Albuminuria increased in WT DOCA-salt (278 ± 55 μg/day) compared with control (17 ± 1 μg/day) and was blunted in the Ephx2−/− DOCA-salt mice (97 ± 23 μg/day). Glomerular nephrin expression demonstrated an inverse relationship with albuminuria. Nephrin immunofluorescence was greater in the Ephx2−/− DOCA-salt group (3.4 ± 0.3 RFU) compared with WT DOCA-salt group (1.1 ± 0.07 RFU). Reduction in renal inflammation and injury was also seen in WT DOCA-salt mice treated with a sEH inhibitor { trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid; tAUCB}, demonstrating that the C-terminal hydrolase domain of the sEH enzyme is responsible for renal protection with DOCA-salt hypertension. These data demonstrate that Ephx2 gene deletion decreases blood pressure, attenuates renal inflammation, and ameliorates glomerular injury in DOCA-salt hypertension.

scholarly journals Soluble Epoxide Hydrolase Inhibition Lowers Arterial Blood Pressure in Angiotensin II Hypertension

Hypertension ◽  
2002 ◽  
Vol 39 (2) ◽  
pp. 690-694 ◽  
Author(s):  
John D. Imig ◽  
Xueying Zhao ◽  
Jorge H. Capdevila ◽  
Christophe Morisseau ◽  
Bruce D. Hammock
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Arterial Blood Pressure ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Arterial Blood

Cerebral hemorrhage and edema following brain biopsy in rats: significance of mean arterial blood pressure

2000 ◽  
Vol 92 (1) ◽  
pp. 100-107 ◽  
Author(s):  
Helene Benveniste ◽  
Katie R. Kim ◽  
Laurence W. Hedlund ◽  
John W. Kim ◽  
Allan H. Friedman
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Neurosurgical Procedures ◽  
Shr Rats ◽  
Mr Microscopy ◽  
Content Type ◽  
Wky Rats ◽  
Arterial Blood ◽  
Fine Print

Object. It is taken for granted that patients with hypertension are at greater risk for intracerebral hemorrhage during neurosurgical procedures than patients with normal blood pressure. The anesthesiologist, therefore, maintains mean arterial blood pressure (MABP) near the lower end of the autoregulation curve, which in patients with preexisting hypertension can be as high as 110 to 130 mm Hg. Whether patients with long-standing hypertension experience more hemorrhage than normotensive patients after brain surgery if their blood pressure is maintained at the presurgical hypertensive level is currently unknown. The authors tested this hypothesis experimentally in a rodent model.Methods. Hemorrhage and edema in the brain after needle biopsy was measured in vivo by using three-dimensional magnetic resonance (MR) microscopy in the following groups: WKY rats, acutely hypertensive WKY rats, spontaneously hypertensive rats (SHR strain), and SHR rats treated with either sodium nitroprusside or nicardipine. Group differences were compared using Tukey's studentized range test followed by individual pairwise comparisons of groups and adjusted for multiple comparisons.There were no differences in PaCO2, pH, and body temperature among the groups. The findings in this study indicated that only acutely hypertensive WKY rats had larger volumes of hemorrhage. Chronically hypertensive SHR rats with MABPs of 130 mm Hg did not have larger hemorrhages than normotensive rats. There were no differences in edema volumes among groups.Conclusions. The brains of SHR rats with elevated systemic MABPs are probably protected against excessive hemorrhage during surgery because of greater resistance in the larger cerebral arteries and, thus, reduced cerebral intravascular pressures.

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