Abstract —Cytochrome P 450 epoxygenases convert arachidonic acid into 4 epoxyeicosatrienoic (EET) regioisomers, which were recently identified as endothelium-derived hyperpolarizing factors in coronary blood vessels. Both EETs and their dihydroxyeicosatrienoic (DHET) metabolites have been shown to relax conduit arteries at micromolar concentrations, whereas the plasma concentrations of are nanomolar range. However, effects DHETs on resistance arterioles not examined. We administered isolated...

Angiotensin II (Ang II) contributes to vascular pathology in part by stimulating NADPH oxidase activity, leading increased formation of superoxide (O2-). We reported that O2- levels, and expression the p47phox subunit are human abdominal aortic aneurysms (AAAs). Here, we tested hypothesis deletion will attenuate oxidative stress AAA Ang II-infused apoE-/- mice.Male apoE-/-p47phox-/- mice received saline or (1000 ng x kg(-1) min(-1)) infusion for 28 days, after which weight maximal diameter...

Abdominal aortic aneurysms (AAAs) in humans are associated with locally increased oxidative stress and activity of NADPH oxidase. We investigated the hypothesis that vitamin E, an antioxidant documented efficacy mice, can attenuate AAA formation during angiotensin II (Ang II) infusion apolipoprotein E-deficient mice.Six-month-old male mice were infused Ang at 1000 ng/kg per minute for 4 weeks via osmotic minipumps while consuming either a regular diet or enriched E (2 IU/g diet). After...

Obesity and insulin resistance (IR) increase the risk for coronary heart disease; however, much of this is not attributable to traditional factors. We sought determine whether weight loss associated with supervised aerobic exercise beneficially alters biomarkers oxidative stress these alterations are improvements in measures resistance. Twenty-five sedentary overweight obese [body mass index (BMI) = 33.0 +/- 0.8 kg/m(2)] individuals, characteristics metabolic syndrome, participated a 4- 7-mo...

Diets enriched in docosahexaenoic acid, a major n-3 fatty acid fish oil, have hypotensive properties. One mechanism that can lower blood pressure is the direct dilation of arterioles by metabolites. Vascular endothelium contains cytochrome P-450 epoxygenases transform n-6 arachidonate into epoxyeicosatrienoic acids (EETs), potent dilators coronary and activators large-conductance calcium-activated potassium (BK(Ca)) channels. To test whether analogous activations occur for docosahexaenoate,...

Epoxyeicosatrienoic acids (EETs) are released from endothelial cells and potently dilate small arteries by hyperpolarizing vascular myocytes. In the present study, we investigated structural specificity of EETs in dilating canine porcine coronary microvessels (50-140 microm ID) activating large-conductance Ca2+-activated K+ (BK(Ca)) channels. The potencies efficacies EET regioisomers enantiomers were compared with those two homologs: epoxyeicosaquatraenoic (EEQs), which made eicosapentaenoic...

The purposes of this study were to determine if coronary dilation secondary an increase in myocardial oxygen consumption (MVO2) affects the microcirculation a homogeneous or heterogeneous manner and comparable degrees produced by increasing MVO2 exogenous (intravenous adenosine) endogenous dipyridamole) adenosine have similar effects microcirculation. epimyocardial was observed through intravital microscope stroboscopic epi-illumination anesthetized open-chest dogs. Aortic pressure heart...

Although morbidity and mortality conferences (MMCs) are meant to promote quality care through careful analysis of adverse events, focus on individual actions or the fear incrimination may interfere with identification system issues contributing outcomes.Participant attitudes before after intervention towards patient safety conference redesign were assessed using an attitudinal survey. A list factors, recommended solutions targeted improvements was maintained ongoing progress...

Resveratrol is a natural phytophenol that exhibits cardioprotective effects. This study was designed to elucidate the mechanisms by which resveratrol protects against diabetes-induced cardiac dysfunction. Normal control ( m-Lepr db ) mice and type 2 diabetic Lepr were treated with orally for 4 wk. In vivo MRI showed improved function increasing left ventricular diastolic peak filling rate in mice. protective role partially explained resveratrol's effects improving nitric oxide (NO)...

We hypothesized that the interaction between tumor necrosis factor-alpha (TNF-alpha)/nuclear factor-kappaB (NF-kappaB) via activation of IKK-beta may amplify one another, resulting in evolution vascular disease and insulin resistance associated with diabetes. To test this hypothesis, endothelium-dependent (ACh) -independent (sodium nitroprusside) vasodilation isolated, pressurized coronary arterioles from mLepr(db) (heterozygote, normal), Lepr(db) (homozygote, diabetic), mice null for...

Type 2 diabetes (T2D) is a leading risk factor for variety of cardiovascular diseases including coronary heart disease and atherosclerosis. Exercise training (ET) has beneficial effect on these disorders, but the basis this not fully understood. This study was designed to investigate whether ET abates endothelial dysfunction in aorta T2D. Heterozygous controls (m Lepr db ) type diabetic mice ( db/db; were either exercise entrained by forced treadmill or remained sedentary 10 wk. Ex vivo...

We tested the hypothesis that atherosclerosis potentiates coronary vasoconstriction to serotonin and ergonovine. Coronary microvascular pressures diameters were measured in beating left ventricle normal atherosclerotic cynomolgus monkeys. Pressures arteries (190–350 microns diam) distal lesions. Microvascular pressure simultaneous measurements of aortic myocardial blood flow used calculate segmental vascular resistance (large artery resistance) during serotonin, phenylephrine, ergonovine...

Myogenic constriction is an important mechanism of blood flow regulation; however, it has never been demonstrated in the human coronary circulation. We examined responses resistance vessels vitro to changes intraluminal pressure and evaluated role protein kinase C (PKC). Microvessels (passive diameter 44-227 microns) were dissected from atrial appendages obtained during cardiac surgery studied under conditions zero flow. In response stepped increases pressure, there was a graded such that at...

The purpose of the present study was to test hypothesis that ATP-sensitive potassium channels mediate autoregulatory vasodilatation coronary arterioles in vivo. Experiments were performed 23 open-chest anesthetized dogs. Coronary arterial microvascular diameters directly measured with fluorescence microangiography using an intravital microscope and stroboscopic epi-illumination synchronized cardiac cycle. A mild stenosis (perfusion pressure = 60 mm Hg), a critical 40 complete artery...

Endothelium-derived hyperpolarizing factor (EDHF) plays a crucial role in modulating vasomotor tone, especially microvessels when nitric oxide-dependent control is compromised such as diabetes. Epoxyeicosatrienoic acids (EETs), potassium ions (K+), and hydrogen peroxide (H2O2) are proposed EDHFs. However, the identity (or identities) of EDHF-dependent endothelial dilators has not been clearly elucidated We assessed mechanisms EDHF-induced vasodilation wild-type (WT, normal), db/db (advanced...

The transgenic (mRen2)27 (Ren2) rat overexpresses mouse renin in extrarenal tissues, causing increased local synthesis of ANG II, oxidative stress, and hypertension. However, little is known about the role stress induced by tissue renin-angiotensin system (RAS) as a contributing factor pulmonary hypertension (PH). Using male Ren2 rats, we test hypothesis that lung RAS overexpression resultant contribute to PH vascular remodeling. Mean arterial pressure (MAP), right ventricular systolic...

We have previously reported chronic low-intensity interval exercise training attenuates fibrosis, impaired cardiac mitochondrial function, and coronary vascular dysfunction in miniature swine with left ventricular (LV) hypertrophy (Emter CA, Baines CP. Am J Physiol Heart Circ 299: H1348-H1356, 2010; Emter et al. 301: H1687-H1694, 2011). The purpose of this study was to test two hypotheses: 1) preserves normal myocardial oxygen supply/demand balance; 2) training-dependent attenuation LV...

Adiponectin (APN) can confer protection against metabolism-related illnesses in organs such as fat, the liver, and skeletal muscle. However, it is unclear whether APN improves endothelial-dependent nitric oxide-mediated vasodilation type 2 diabetes and, if so, by what mechanism. We tested exogenous delivery endothelial function diabetic mice explored mechanisms underlying observed improvement. To test hypothesis, we injected adenovirus (Ad-APN) or β-galactosidase (Ad-βgal; control virus) via...

Weight loss improves metabolic syndrome (MetS) factors, but risk may return with weight regain. This study was designed to determine if exercise training can maintain improvements in MetS factors during In a randomized control trial,102 overweight or obese (body mass index 25.0-39.9 kg/m(2)) men and women (age 21-52 yr), characteristics of the MetS, lost 10% body supervised walking/jogging at 60% maximal oxygen consumption (Vo(2 max)) (-400 kcal/session), 5 days/wk, caloric restriction (-600...