| Reversal of fructose-induced hypertension and insulin resistance by chronic losartan treatment is independent of AT2 receptor activation in rats. | |
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MedLine Citation:
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PMID: 16269963 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: To examine whether angiotensin II type 2 receptors (AT2R) are involved in the reversal of fructose-induced hypertension and insulin resistance after chronic angiotensin II type 1 receptor (AT1R) blockade. METHODS: Sprague-Dawley rats on fructose-enriched or regular diets were pretreated with losartan, an AT1R antagonist, or vehicle for 2 weeks before two-step glucose and insulin clamp experiments with [3-3H]glucose infusion. The hepatic glucose production (HGP) and whole-body glucose uptake (WBGU) were calculated during basal, euglycemic and euglycemic hyperinsulinemic periods. Blood pressure was measured before and after acute losartan (10 mg/kg, i.v. bolus), alone or in combination of PD123319 (PD, 50 microg/kg per min), an AT2R antagonist, or CGP42112 (2 microg/kg per min), an AT2R agonist, during the clamp study. RESULTS: In rats on a regular diet, acute infusion of losartan alone or in combination with PD, an AT2R blocker, did not alter blood pressure and glucose metabolism during experiments. Fructose feeding for 6 weeks significantly increased blood pressure and attenuated insulin-mediated suppression of HGP and stimulation of WBGU. Both acute and chronic administration of losartan suppressed fructose-induced hypertension. Concomitant treatment with PD and losartan blunted the acute but not chronic losartan-mediated depressor effect. Acute losartan treatment further reduced insulin-induced suppression of HGP, but simultaneously increased insulin-stimulated WBGU. These acute metabolic effects of losartan were eliminated when PD was co-administered with losartan. Conversely, chronic losartan pretreatment significantly enhanced suppression of HGP and increased stimulation of WBGU by insulin, which were not altered when PD or CGP 42112 was superimposed on losartan during the clamp experiments. CONCLUSIONS: These results suggest that reversal of high fructose-induced hypertension and insulin resistance by chronic losartan treatment is not dependent on AT2R activation and that functional activation of AT1R plays a major role in the pathogenesis of high fructose-induced hypertension and insulin resistance. |
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Authors:
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Po-Shiuan Hsieh |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of hypertension Volume: 23 ISSN: 0263-6352 ISO Abbreviation: J. Hypertens. Publication Date: 2005 Dec |
Date Detail:
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Created Date: 2005-11-04 Completed Date: 2006-03-02 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8306882 Medline TA: J Hypertens Country: England |
Other Details:
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Languages: eng Pagination: 2209-17 Citation Subset: IM |
Affiliation:
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Department of Physiology and Biophysics, National Defense Medical Center, National Defense University, Taipei, Taiwan. pshsieh@hotmail.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II Type 1 Receptor Blockers
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administration & dosage,
pharmacology Animals Antihypertensive Agents / administration & dosage, pharmacology Fructose / toxicity* Glucose / metabolism Glucose Clamp Technique Hypertension / chemically induced*, drug therapy*, metabolism Imidazoles / administration & dosage Insulin Resistance Liver / drug effects, metabolism Losartan / administration & dosage, pharmacology* Male Oligopeptides / administration & dosage Pyridines / administration & dosage Rats Rats, Sprague-Dawley Receptor, Angiotensin, Type 2 / agonists, antagonists & inhibitors, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin II Type 1 Receptor Blockers; 0/Antihypertensive Agents; 0/Imidazoles; 0/Oligopeptides; 0/Pyridines; 0/Receptor, Angiotensin, Type 2; 114798-26-4/Losartan; 127060-75-7/CGP 42112A; 130663-39-7/PD 123319; 30237-26-4/Fructose; 50-99-7/Glucose |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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