| AMP-activated protein kinase activator AICAR acutely lowers blood pressure and relaxes isolated resistance arteries of hypertensive rats. | |
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MedLine Citation:
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PMID: 22306847 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVES:: AMP-activated protein kinase (AMPK) activity may alter blood pressure by directly influencing vascular tone. The purpose of this study is to examine if these effects occur acutely in a model of hypertension. METHODS AND RESULTS:: Using distinct groups of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) we compare baseline aortic and mesenteric artery AMPK activation (by immunoblotting), hemodynamic (blood pressure and heart rate via carotid catheter) and biochemical responses to an acute injection of AMPK activator 5-aminoimidazole-4-carboxyamide-1-β-D-ribofuranoside (AICAR) in vivo and vasomotor responses of isolated mesenteric vessels to AICAR exposure in vitro using myography. Mean arterial pressure (MAP) decreased from 196 ± 3 to 122 ± 15 mmHg (P < 0.001) during the 30 min following AICAR injection in SHR (an effect partially prevented by NOS inhibitor L-NAME), but in WKY MAP was unaffected by AICAR. Basal AMPK activation (phosphorylation of AMPK activation site threonine 172) was reduced by approximately 50% in aorta of SHR vs. WKY (0.49 ± 0.1 vs. 1.0 ± 0.1 arbitrary units, P < 0.001), and was improved approximately 1.6-fold in SHR but not in WKY aorta 30 min following AICAR injection. In isolated vessel experiments, dose-dependent vasorelaxation to AICAR was similar in mesenteric arteries of SHR and WKY, although responses were more reliant on nitric oxide in SHR vs. WKY. CONCLUSIONS:: The ability of AICAR to improve vascular AMPK activation, and to generate parallel reductions in blood pressure and relaxation of SHR resistance vasculature, highlights the potential importance of AMPK in the regulation of blood pressure and vascular tone. |
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Authors:
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Rebecca J Ford; Susan R Teschke; E Benjamin Reid; Kristina K Durham; Jeffrey T Kroetsch; James W E Rush |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-2 |
Journal Detail:
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Title: Journal of hypertension Volume: - ISSN: 1473-5598 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8306882 Medline TA: J Hypertens Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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