Significance This study provides molecular evidence indicating that female hormone/estrogen enables inhibition of vascular soluble epoxide hydrolase (sEH) expression in physiological conditions via an epigenetic-based regulatory mechanism, leading to increase the level epoxyeicosatrienoic acids (EETs) that: ( i ) possess cardio-protective properties, such as vasodilation, resulting better blood supply tissues and lower pressure, ii are degraded/inactivated by sEH. To this end, increases...

Hypoxia appears to promote contraction [hypoxic pulmonary vasoconstriction (HPV)] of bovine arteries (BPA) through removal a peroxide-mediated relaxation. This study examines the roles BPA Nox oxidases and mitochondria in HPV response. Inhibitors Nox2 (0.1 mM apocynin 50 μM gp91-dstat) mitochondrial electron transport (10 antimycin rotenone) decreased superoxide generation without affecting 25 KCl or Transfection with small inhibitory RNA (siRNA) for Nox4 protein expression, respectively,...

Age-dependent alteration of the renin-angiotensin system (RAS) and generation angiotensin II (Ang II) are well documented. By contrast, RAS-independent Ang in aging its responses to exercise have not been explored. To this end, we examined effects chymase, a secretory serine protease, on angiotensin-converting enzyme (ACE)-independent conversion I II. We hypothesized that age-dependent cardiac formation is chymase dependent nature prevented by training. Experiments were conducted hearts...

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We have previously provided evidence that hydrogen peroxide (H 2 O ) stimulates soluble guanylate cyclase (sGC) under conditions where it relaxes isolated endothelium-removed bovine pulmonary arteries (BPAs). Since was recently reported H induces coronary vasorelaxation associated with a nitric oxide/cGMP-independent thiol oxidation/subunit dimerization-elicited activation of protein kinase G (PKG), we investigated whether this mechanism participates in the relaxation BPAs to . precontracted...

The activity of glucose-6-phosphate dehydrogenase (G6PD) controls a vascular smooth muscle relaxing mechanism promoted by the oxidation cytosolic NADPH, which has been associated with activation 1α form protein kinase G (PKG-1α) thiol oxidation-elicited subunit dimerization. This PKG-1α-activation appears to contribute responses isolated endothelium-removed bovine pulmonary arteries (BPA) elicited peroxide, NADPH resulting from G6PD inhibition, and hypoxia. Dehydroepiandrosterone (DHEA) is...

To test the hypothesis that epoxyeicosatrienoic acids (EETs) facilitate pulmonary responses to hypoxia, male wild-type (WT) and soluble-epoxide hydrolase knockout (sEH-KO) mice, WT mice chronically fed a sEH inhibitor (t-TUCB; 1 mg·kg-1·day-1) were used. Right ventricular systolic pressure (RVSP) was recorded under control hypoxic conditions. The RVSP comparable among all groups. However, hypoxia elicited increases in groups with predominance sEH-KO t-TUCB-treated mice. 14,15-EEZE (an EET...

Endothelium-denuded bovine pulmonary arteries (BPA) contract to hypoxia through a mechanism potentially involving removing superoxide-derived hydrogen peroxide-mediated relaxation. BPA organ cultured for 24 h with 0.1 mM cobalt chloride (CoCl 2 ) increase the expression and activity of heme oxygenase-1 (HO-1) is accompanied by decrease in 5 μM lucigenin-detectable superoxide an horseradish peroxidase-luminol detectable peroxide levels. Force development KCl was not affected increases HO-1,...

We previously reported that isolated endothelium-removed bovine pulmonary arteries (BPAs) contract to hypoxia associated with removal of peroxide- and cGMP-mediated relaxation. In contrast, coronary (BCAs) relax cytosolic NADPH oxidation coordinating multiple relaxing mechanisms. Since we recently found H(2)O(2) relaxes BPAs through PKG activation by both soluble guanylate cyclase (sGC)/cGMP-dependent cGMP-independent thiol oxidation/subunit dimerization mechanisms, investigated if these...

The activity of glucose-6-phosphate dehydrogenase (G6PD) appears to control a vascular smooth muscle relaxing mechanism regulated through cytosolic NADPH oxidation. Since our recent studies suggest that thiol oxidation-elicited dimerization the 1α form protein kinase G (PKG1α) contributes relaxation isolated endothelium-removed bovine pulmonary arteries (BPA) peroxide and responses hypoxia, we investigated whether oxidation promoted by PKG1α dimerization. Relaxation BPA G6PD inhibitors...

The biological role of epoxyeicosatrienoic acids (EETs) in the regulation pulmonary circulation is currently under debate. We hypothesized that EETs initiate increases right ventricular systolic pressure (RVSP) via perhaps, vasoconstriction. Mice were anesthetized with isoflurane. Three catheters, inserted into left jugular vein, carotid artery, and used for infusing EETs, monitoring blood (BP), RVSP respectively. BP continuously recorded at basal conditions, response to administration 4...

The direct impact of de novo synthesis homocysteine (Hcy) and its reactive metabolites, Hcy-S-S-Hcy Hcy thiolactone (HCTL), on vascular function has not been fully elucidated. We hypothesized that synthesized within endothelial cells affects activity angiotensin-converting enzyme (ACE) by homocysteinylation amino- and/or sulfhydryl moieties. This covalent modification enhances ACE reactivity toward angiotensin II (ANG II)-NADPH oxidase-superoxide-dependent dysfunction. Mesenteric coronary...

We hypothesized that potentiating the bioavailability of endothelial epoxyeicosatrienoic acids (EETs) via deletion gene for soluble epoxide hydrolase (sEH), or downregulation sEH expression, enhances flow/shear stress-induced dilator responses (FID) arterioles. With use male (M) and female (F) wild-type (WT) sEH-knockout (KO) mice, isolated gracilis muscle arterioles were cannulated pressurized at 80 mmHg. Basal tone increases in diameter as a function perfusate flow (5, 10, 15, 20, 25...

We tested the hypothesis that suppression of epoxyeicosatrienoic acid (EET) metabolism via genetic knockout gene for soluble epoxide hydrolase (sEH-KO), or female-specific downregulation sEH expression, plays a role in potentiation pulmonary hypertension. used male (M) and female (F) wild-type (WT) sEH-KO mice; latter have high EETs. Right ventricular systolic pressure (RVSP) mean arterial blood (MABP) control response to vivo administration U46619 (thromboxane analog), 14,15-EET, 14,15-EEZE...

Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid via CYP/epoxygenases, which catabolized by soluble epoxide hydrolase (sEH) and known to possess cardioprotective properties. To date, the role sEH in modulation pressure-induced myogenic response/constriction coronary arteries, an important regulatory mechanism circulation, issue as whether disruption gene affects response sex differentially have never been addressed. this end, experiments were conducted on male (M) female...

Epoxyeicosatrienoic acids (EETs) are cardioprotective mediators metabolized by soluble epoxide hydrolase (sEH) to form corresponding diols (DHETs). As a sex-susceptible target, sEH is involved in the sexually dimorphic regulation of cardiovascular function. Thus, we hypothesized that female sex favors EET-mediated potentiation cardiac function via downregulation expression, followed upregulation peroxisome proliferator-activated receptors (PPARs). Hearts were isolated from male (M) and (F)...

Roles of soluble epoxide hydrolase (sEH), the enzyme responsible for hydrolysis epoxyeicosatrienoic acids (EETs) to their diols (DHETs), in coronary circulation and cardiac function remain unknown. We tested hypothesis that compromising EET hydrolysis/degradation, via sEH deficiency, lowers resistance promote perfusion function. Hearts were isolated from wild type (WT), knockout (KO) mice WT chronically treated with t-TUCB (sEH inhibitor), perfused constant flow at different pre-loads....

The roles of ACE-independent ANG II production via chymase and therapeutic potential epoxyeicosatrienoic acids (EETs) in fructose-induced metabolic syndrome (MetS) the adolescent population remain elusive. Thus we tested hypothesis that a high-fructose diet (HFD) young rats elicits chymase-dependent increases oxidative stress, responses are reversible by 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), an inhibitor soluble epoxide hydrolase (sEH) metabolizes EETs. Three...

The endothelial glycocalyx (EG) is degraded early during sepsis, and currently available treatments are not effective in promptly restoring it. Here, we created liposomal nanocarriers of preassembled (LNPG) by synthesizing glycosylated syndecan-1 inserting it into the lipid membrane unilamellar liposomes. We hypothesized that LNPG would fuse with cells where EG restore sepsis. induced endotoxemia C57BL/6J mice using lipopolysaccharides (LPS) treated them LNPG, saline, syndecan-1, or...

Mild hyperhomocysteinemia (HHcy, clinically defined as less than 30 μmol/L) is an independent cardiovascular disease (CVD) risk factor, and associated with many complications during pregnancy, such preeclampsia (PE). The aim of this study was to assess the effect long-term mild HHcy on cardiac metabolic function multiparous rats. Female rats were mated 3 4 times fed methionine in drinking water increase plasma Hcy (2.9 ± 0.3 10.5 2.3 until termination. This caused significant heart...

Ferrochelatase (FECH) is an enzyme necessary for heme synthesis, which essential maintaining normal functions of endothelial nitric oxide synthase (eNOS) and soluble guanylyl cyclase (sGC). We tested the hypothesis that inhibition vascular FECH to attenuate synthesis downregulates eNOS sGC expression, resulting in impaired NO/cGMP-dependent relaxation. To this end, isolated bovine coronary arteries (BCAs) were vitro incubated without (as controls) or with N-methyl protoporphyrin (NMPP;...

Subarachnoid hemorrhage is a serious clinical condition that impairs local cerebral blood flow perfusion and consequently initiates neuronal dysfunction. Pressure-sensitive myogenic vasomotor regulation an important mechanism involved in the of flow. We hypothesized extravascular hemolyzed enhances arteriolar constriction, which vivo may contribute to reduction after subarachnoid hemorrhage.