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Author  |
Nicol, C.J.; Adachi, M.; Akiyama, T.E.; Gonzalez, F.J. |
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Title |
PPARgamma in endothelial cells influences high fat diet-induced hypertension |
Type |
Journal Article |
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Year |
2005 |
Publication |
American journal of hypertension : journal of the American Society of Hypertension |
Abbreviated Journal |
Am J Hypertens |
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Volume |
18 |
Issue |
4 Pt 1 |
Pages |
549-556 |
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Keywords |
Administration, Oral; Animals; Antihypertensive Agents/pharmacology; Blood Pressure/drug effects; Diabetes Mellitus, Type 2/physiopathology; Dietary Fats/*administration & dosage/pharmacology; Dose-Response Relationship, Drug; Endothelial Cells/*metabolism; Female; Heart Rate/drug effects; Hypertension/*etiology; Ligands; Male; Mice; Mice, Knockout; PPAR gamma/*metabolism; Sodium Chloride/administration & dosage/pharmacology; Thiazolidinediones/pharmacology |
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Abstract |
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands improve human hypertension. However, the mechanism and site of this effect remains unknown, confounded by PPARgamma expression in many cell types, including endothelial cells (ECs). METHODS: To evaluate the vascular role of PPARgamma we used a conditional null mouse model. Specific disruption of PPARgamma in ECs was created by crossing Tie2-Cre+ transgenic (T2T+) and PPARgamma-floxed (fl/fl) mice to generate PPARgamma (fl/fl)T2T+ (PPARgamma E-null) mice. Conscious 8- to 12-week-old congenic PPARgamma (fl/fl)Cre- (wild type) and PPARgamma E-null mice were examined for changes in systolic blood pressure (BP) and heart rate (HR), untreated, after 2 months of salt-loading (drinking water), and after treatment for 3 months with high fat (HF) diet alone or supplemented during the last 2 weeks with rosiglitazone (3 mg/kg/d). RESULTS: Untreated PPARgamma E-nulls were phenotypically indistinguishable from wild-type littermates. However, compared to similarly treated wild types, HF-treated PPARgamma E-nulls had significantly elevated systolic BP not seen after normal diet or salt-loading. Despite sex-dependent baseline differences, salt-loaded and HF-treated PPARgamma E-nulls of either sex had significantly elevated HR versus wild types. Interestingly, rosiglitazone improved serum insulin levels, but not HF diet-induced hypertension, in PPARgamma E-null mice. CONCLUSIONS: These results suggest that PPARgamma in ECs not only is an important regulator of hypertension and HR under stressed conditions mimicking those arising in type 2 diabetics, but also mediates the antihypertensive effects of rosiglitazone. These data add evidence supporting a beneficial role for PPARgamma-specific ligands in the treatment of hypertension, and suggest therapeutic strategies targeting ECs may prove useful. |
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Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA |
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English |
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ISSN |
0895-7061 |
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Notes |
PMID:15831367 |
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no |
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Call Number |
refbase @ user @ |
Serial |
69 |
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Author |
Ziegler, W.H. |
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Title |
[Endocrinological studies in arterial hypertension. Search for phaeochromocytoma] |
Type |
Journal Article |
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Year |
1976 |
Publication |
Schweizerische Medizinische Wochenschrift |
Abbreviated Journal |
Schweiz Med Wochenschr |
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Volume |
106 |
Issue |
34 |
Pages |
1148-1150 |
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Keywords |
Angiography; Blood Volume; Catecholamines/urine; Glucagon/diagnostic use; Histamine/diagnostic use; Humans; Hydrogen-Ion Concentration; Hypertension/*etiology; Methods; Pheochromocytoma/*complications/diagnosis; Tyramine/diagnostic use |
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Abstract |
Elevated urinary catecholamines and their metabolites are the only findings which confirm the presence of pheochromocytoma. This examination is of particular interest if carried out in urine produced after spontaneous hypertensive episodes. Pharmacologic tests when carried out under standard conditions have proven to be a reliable aid in cases of suspected pheochromocytoma. Roentgenographic studies, determination of local plasma catecholamine concentrations and blood volume control should be undertaken in these patients before surgical procedure. |
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German |
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Original Title |
Endokrinologische Untersuchungen bei arterieller Hypertonie. Suche nach Phaochromozytom |
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0036-7672 |
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Notes |
PMID:12561 |
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Call Number |
Equine Behaviour @ team @ |
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4047 |
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