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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 |
Colahan, P.; Lindsey, E.; Nunier, C. |
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Title |
Determination of the center of pressure of the hoofs of the forelimbs of horses standing on a flat level surface |
Type |
Journal Article |
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Year |
1993 |
Publication |
Acta Anatomica |
Abbreviated Journal |
Acta Anat (Basel) |
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Volume |
146 |
Issue |
2-3 |
Pages |
175-178 |
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Keywords |
Animals; Forelimb/*physiology; Hoof and Claw/*physiology; Horses/*physiology; *Posture; Pressure |
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Abstract |
The pressure exerted on a flat level surface by recently trimmed, unshod hoofs of the front limbs of 23 sound, adult horses was measured using pressure-sensitive film and a specially built cassette. The horses were tranquilized and stood with one foot on the 2.9-cm-thick cassette and the other on a block of equal height. The hoofs were observed for motion during the measurement, and the developed film was examined for improper alignment of the film or slipping of the hoof. The center of pressure was located using the method of weighted proportions of Barrey. This static measurement system with a long measurement time and the number of measurements reduced the influence of variables inherent in the horses' behavior and the measuring system. The calculated point was recorded as falling medial to, lateral to or on a line bisecting the central sulcus of the frog. In the dorsal to palmar orientation the point was classified with reference to a line drawn halfway between the most dorsal and the most palmar mark on the film. Forty-six percent of the calculated centers of pressure were located in the medial heel area. Binomial analysis for large samples indicates that this was a significant variation from a random distribution. Seventy-six percent of the centers were located in or on the borders of the medial heel. |
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College of Veterinary Medicine, University of Florida, Gainesville 32608-0136 |
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English |
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0001-5180 |
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Notes |
PMID:8470462 |
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Call Number |
refbase @ user @ |
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1946 |
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