| Cardiovascular interactions between losartan and fructose in mice. | |
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MedLine Citation:
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PMID: 19995939 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIM: To determine whether pharmacological blockade of angiotensin (Ang) AT1 receptors alters the cardiovascular, metabolic, and angiotensin-converting enzyme (ACE and ACE2) responses to a fructose diet in mice. METHODS: C57BL male mice were fed with a 60% fructose diet for 8 weeks in combination with losartan treatment on week 9 (30 mg/kg per day). Blood pressure (BP), heart rate (HR), and autonomic balance were monitored using radiotelemetry with spectral analysis. Renal ACE and ACE2 activity and protein levels as well as Ang II and Ang 1-7 were measured. RESULTS: Fructose impaired glucose tolerance and increased plasma cholesterol and insulin. These effects were not corrected by losartan treatment. Fructose increased BP and HR but only during the dark period. Short-term losartan treatment decreased BP by 16% in the fructose group but had no effect in controls. This was accompanied by a decrease in BP variance and its low-frequency component. Fructose increased Ang II (plasma and kidney) and ACE 2 (renal activity and protein expression). Losartan alone increased plasma Ang II in plasma and ACE2 in kidney. There were no changes in renal Ang 1-7 levels. CONCLUSIONS: Losartan reversed the pressor effect of a high fructose diet, demonstrating that there are prominent interactions between a dietary regimen that produces glucose intolerance and an antihypertensive drug that antagonizes Ang signaling. The mechanism of change may be via renal Ang II rather than the ACE2/Ang 1-7 pathway because the fructose losartan combination resulted in lowered renal Ang II without changes in Ang 1-7. |
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Authors:
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Danielle Senador; Mary Key; K Bridget Brosnihan; Maria Claudia Irigoyen; Khalid M Elased; Mariana Morris |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural Date: 2009-12-07 |
Journal Detail:
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Title: Journal of cardiovascular pharmacology and therapeutics Volume: 15 ISSN: 1940-4034 ISO Abbreviation: J. Cardiovasc. Pharmacol. Ther. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-02-05 Completed Date: 2010-04-22 Revised Date: 2012-04-12 |
Medline Journal Info:
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Nlm Unique ID: 9602617 Medline TA: J Cardiovasc Pharmacol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 68-77 Citation Subset: IM |
Affiliation:
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Wright State University, Boonshoft School of Medicine, Dayton, OH 45435, USA. mariana.morris@wright.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Antihypertensive Agents / pharmacology* Blood Pressure / drug effects Blotting, Western Cardiovascular Physiological Phenomena / drug effects* Cholesterol / blood Disease Models, Animal Drug Interactions Fructose / pharmacology* Heart Rate / drug effects Insulin / blood Kidney / metabolism Losartan / pharmacology* Male Mice Mice, Inbred C57BL Peptidyl-Dipeptidase A / metabolism* Receptor, Angiotensin, Type 1 / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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DK59630/DK/NIDDK NIH HHS; P01 HL051952-18/HL/NHLBI NIH HHS; R01HL69319/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Insulin; 0/Receptor, Angiotensin, Type 1; 114798-26-4/Losartan; 30237-26-4/Fructose; 57-88-5/Cholesterol; EC 3.4.15.1/Peptidyl-Dipeptidase A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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