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Conference Paper: Heterozygous endothelial endothelin-1 overexpression potentiates endothelium-dependent contractions in the carotid arteries of obese mice

TitleHeterozygous endothelial endothelin-1 overexpression potentiates endothelium-dependent contractions in the carotid arteries of obese mice
Authors
KeywordsEndothelium
Endothelin
Obesity
Issue Date2013
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.shef-ac-press.co.uk
Citation
The 2013 High Blood Pressure Research Scientific Sessions (HBPR 2013), New Orleans, LA., 11-14 September 2013. In Hypertension, 2013, v. 62 n. 3 Meeting Abstracts, abstract 643 How to Cite?
AbstractElevated plasma levels of the vasoconstrictor peptide endothelin-1 (ET-1) are associated with cardiovascular risk factors such as obesity, diabetes and hypertension, in which endothelium-dependent contractions are prominent. Exogenous ET-1 promotes the release of endothelium-derived contracting factors (EDCF), but the role of endogenously produced ET-1 in these processes is unknown. Therefore, mice with tie-1 promoter driven endothelium-restricted heterozygous overexpression of ppET-1 (TET+/-) and WT littermates were kept on standard chow as lean controls or administered a high fat diet for 30 weeks to induce obesity. At sacrifice, fasting glucose levels were significantly elevated in obese animals (8.3±0.3 vs. 5.3±0.2 mmol/l in lean controls, n=6, P<0.001). Isometric tension was measured in aortic and carotid arterial rings in wire myographs. In phenylephrine-contracted aortic rings, endothelium-dependent and –independent relaxations to acetylcholine and sodium nitroprusside, respectively, were unaltered between groups. In carotid arteries, the potency of phenylephrine to evoke contractions was greater in preparations from obese TET+/- mice (pD2 6.71±0.07 vs. lean TET+/- 6.34±0.13, n=5-6, P<0.05), whereas there was no change in the contractile response to the α1-adrenergic agonist by diet-induced obesity in WT littermates. The augmented EDCF responses to acetylcholine of quiescent carotid arterial rings of obese animals were further potentiated by TET+/- (Emax 51.3±1.1% vs. 40.6±1.3% KCl in WT obese, n=6, P<0.001). The production of 6-keto PGF1α – the stable metabolite of prostacyclin – was increased significantly in preparations from obese TET+/- mice (238.4±30.0 vs. 127.0±12.7 pg/mL in obese WT littermates, n=4-6, P<0.05). In the presence of L-NAME, TP receptor activation by U46619 was more effective in obese TET+/- (Emax 151.8±5.4% vs. 126.1±4.7% KCl in WT obese, n=4-6, P<0.05). Overall, TET+/- had no effect on relaxations in obese animals, but contractile responses – EDCF-mediated ones in particular – were facilitated. The present results suggest that this is due to an increased production of vasoconstrictor prostanoids possibly combined with an augmented responsiveness of the underlying vascular smooth muscle.
DescriptionPoster Session II: abstract 643
This journal suppl. published Abstracts From the American Heart Association's High Blood Pressure Research 2013 Scientific Sessions
Persistent Identifierhttp://hdl.handle.net/10722/203722
ISSN
2015 Impact Factor: 6.294
2015 SCImago Journal Rankings: 3.702

 

DC FieldValueLanguage
dc.contributor.authorBaretella, OMen_US
dc.contributor.authorChung, SKen_US
dc.contributor.authorXu, Aen_US
dc.contributor.authorVanhoutte, PMen_US
dc.date.accessioned2014-09-19T16:11:30Z-
dc.date.available2014-09-19T16:11:30Z-
dc.date.issued2013en_US
dc.identifier.citationThe 2013 High Blood Pressure Research Scientific Sessions (HBPR 2013), New Orleans, LA., 11-14 September 2013. In Hypertension, 2013, v. 62 n. 3 Meeting Abstracts, abstract 643en_US
dc.identifier.issn0194-911X-
dc.identifier.urihttp://hdl.handle.net/10722/203722-
dc.descriptionPoster Session II: abstract 643-
dc.descriptionThis journal suppl. published Abstracts From the American Heart Association's High Blood Pressure Research 2013 Scientific Sessions-
dc.description.abstractElevated plasma levels of the vasoconstrictor peptide endothelin-1 (ET-1) are associated with cardiovascular risk factors such as obesity, diabetes and hypertension, in which endothelium-dependent contractions are prominent. Exogenous ET-1 promotes the release of endothelium-derived contracting factors (EDCF), but the role of endogenously produced ET-1 in these processes is unknown. Therefore, mice with tie-1 promoter driven endothelium-restricted heterozygous overexpression of ppET-1 (TET+/-) and WT littermates were kept on standard chow as lean controls or administered a high fat diet for 30 weeks to induce obesity. At sacrifice, fasting glucose levels were significantly elevated in obese animals (8.3±0.3 vs. 5.3±0.2 mmol/l in lean controls, n=6, P<0.001). Isometric tension was measured in aortic and carotid arterial rings in wire myographs. In phenylephrine-contracted aortic rings, endothelium-dependent and –independent relaxations to acetylcholine and sodium nitroprusside, respectively, were unaltered between groups. In carotid arteries, the potency of phenylephrine to evoke contractions was greater in preparations from obese TET+/- mice (pD2 6.71±0.07 vs. lean TET+/- 6.34±0.13, n=5-6, P<0.05), whereas there was no change in the contractile response to the α1-adrenergic agonist by diet-induced obesity in WT littermates. The augmented EDCF responses to acetylcholine of quiescent carotid arterial rings of obese animals were further potentiated by TET+/- (Emax 51.3±1.1% vs. 40.6±1.3% KCl in WT obese, n=6, P<0.001). The production of 6-keto PGF1α – the stable metabolite of prostacyclin – was increased significantly in preparations from obese TET+/- mice (238.4±30.0 vs. 127.0±12.7 pg/mL in obese WT littermates, n=4-6, P<0.05). In the presence of L-NAME, TP receptor activation by U46619 was more effective in obese TET+/- (Emax 151.8±5.4% vs. 126.1±4.7% KCl in WT obese, n=4-6, P<0.05). Overall, TET+/- had no effect on relaxations in obese animals, but contractile responses – EDCF-mediated ones in particular – were facilitated. The present results suggest that this is due to an increased production of vasoconstrictor prostanoids possibly combined with an augmented responsiveness of the underlying vascular smooth muscle.-
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.shef-ac-press.co.uk-
dc.relation.ispartofHypertensionen_US
dc.subjectEndothelium-
dc.subjectEndothelin-
dc.subjectObesity-
dc.titleHeterozygous endothelial endothelin-1 overexpression potentiates endothelium-dependent contractions in the carotid arteries of obese miceen_US
dc.typeConference_Paperen_US
dc.identifier.emailChung, SK: skchung@hkucc.hku.hken_US
dc.identifier.emailXu, A: amxu@hku.hken_US
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_US
dc.identifier.authorityChung, SK=rp00381en_US
dc.identifier.authorityXu, A=rp00485en_US
dc.identifier.authorityVanhoutte, PM=rp00238en_US
dc.identifier.hkuros238790en_US
dc.identifier.volume62-
dc.identifier.issue3 Meeting Abstracts-
dc.publisher.placeUnited States-

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