| Increasing peripheral insulin sensitivity by protein tyrosine phosphatase 1B deletion improves control of blood pressure in obesity. | |
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MedLine Citation:
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PMID: 23045458 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Obesity is a major risk factor for hypertension. The copresentation of hypertension and insulin resistance (IR) suggests a role for IR in blood pressure (BP) dysregulation. To test this hypothesis, peripheral IR has been genetically subtracted in a model of obesity by crossing leptin receptor mutant mice (K(db)H(PTP)) with mice lacking protein tyrosine phosphatase 1B (insulin desensitizer, H(db)K(PTP)) to generate obese insulin-sensitive mice (K(db)K(PTP)). BP was recorded in lean (H(db)H(PTP), H(db)K(PTP)) and obese (K(db)H(PTP), K(db)K(PTP)) mice via telemetry, and a frequency analysis of the recording was performed to determine BP variability. Correction of IR in obese mice normalized BP values to baseline levels (H(db)H(PTP): 116 ± 2 mm Hg; K(db)H(PTP): 129 ± 4 mm Hg; K(db)K(PTP): 114 ± 5 mm Hg) and restored BP variability by decreasing its standard deviation and the frequency of BP values over the upper autoregulatory limit of the kidneys. However, although IR-induced increases in proteinuria (versus 53 ± 13 μg/d, H(db)H(PTP)) were corrected in K(db)K(PTP) (112 ± 39 versus 422 ± 159 μg/d, K(db)H(PTP)), glomerular hypertrophy was not. IR reduced plasma aldosterone levels ruling out a role for mineralocorticoids in the development of hypertension. Taken together, these data indicate that correction of IR prevents hypertension, BP variability, and microalbuminuria in obese mice. Although the mechanism remains to be fully determined, increases in aldosterone or sympathoactivation of the cardiovascular system seem to be less likely contributors. |
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Authors:
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Eric J Belin de Chantemèle; Mohammed Irfan Ali; James D Mintz; William E Rainey; Michel L Tremblay; David J Fulton; David W Stepp |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-10-08 |
Journal Detail:
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Title: Hypertension Volume: 60 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-10-18 Completed Date: 2013-01-10 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 1273-9 Citation Subset: IM |
Affiliation:
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Vascular Biology Center, Georgia Health Sciences University, Augusta, GA 30912, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic alpha-1 Receptor Agonists
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pharmacology Albuminuria / genetics, physiopathology Aldosterone / blood Animals Blood Pressure / drug effects, genetics*, physiology Dose-Response Relationship, Drug Female Ganglionic Blockers / pharmacology Heart Rate / genetics, physiology Hypertension / genetics, physiopathology Hypertrophy Insulin Resistance / genetics* Kidney Glomerulus / metabolism, pathology, physiopathology Male Mecamylamine / pharmacology Mesenteric Arteries / drug effects, physiopathology Mice Mice, Inbred C57BL Mice, Knockout Obesity / genetics*, physiopathology Phenylephrine / pharmacology Protein Tyrosine Phosphatase, Non-Receptor Type 1 / deficiency, genetics* Receptors, Leptin / deficiency, genetics Sympathetic Nervous System / drug effects, physiopathology Vasoconstriction / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL092446/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic alpha-1 Receptor Agonists; 0/Ganglionic Blockers; 0/Receptors, Leptin; 52-39-1/Aldosterone; 59-42-7/Phenylephrine; 60-40-2/Mecamylamine; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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