| A possible correlation between the correction of endothelial dysfunction and normalization of high blood pressure levels by 1,3,4-oxadiazole derivative, an L-type Ca2+ channel blocker in deoxycorticosterone acetate and N(G)-nitro-l-arginine hypertensive rats. | |
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MedLine Citation:
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PMID: 19912999 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have previously demonstrated the vasorelaxant activity of 1,3,4-oxadiazole derivative (NOX-1) through L-type Ca2+ channel blockage. In the present study, we investigated whether the correction of endothelial dysfunction is dependent on the normalization of high blood pressure levels by 1,3,4-oxadiazole derivative (NOX-1) in deoxycorticosterone acetate (DOCA-salt) and N(G)-nitro-l-arginine (L-NNA) hypertensive rats. In DOCA-salt and L-NNA hypertensive rats, the mean systolic blood pressure (MSBB) was 185.3+/-4.7 and 170.2+/-4.1 mmHg, whereas after administration of NOX-1 to hypertensive rats, MSBB was 127.8+/-4.5 and 120.2+/-5.1 mmHg, respectively. To study the endothelial dysfunction, concentration-response curves of norepinephrine (NE) and acetylcholine (Ach) were constructed in rat aortic rings isolated from normotensive, hypertensive (DOCA and L-NNA) and NOX-1 treated rats. NE-induced contractions and Ach-induced relaxations were significantly (p<0.05) decreased and increased, respectively in the aorta of NOX-1 treated rats. Vasorelaxant activity of NOX-1 was not abolished by pretreatment of aortic rings with L-NNA, 1H-[1,2,4] oxadiazolo [4,3-A] quinoxalin-1-one (ODQ), indomethacin or glibenclamide. The results suggest that the endothelial dysfunction can be corrected by the L-type Ca2+ channel blocker with endothelium-independent action and that is dependent on the normalization of high blood pressure levels. The antihypertensive and vasorelaxant effects of NOX-1 are mainly endothelial-independent and it can be used to treat hypertension, a state associated with endothelial dysfunction. |
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Authors:
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Girish R Bankar; Gopalan Kutty Nampurath; Pawan G Nayak; Shoumyo Bhattacharya |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-11 |
Journal Detail:
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Title: Chemico-biological interactions Volume: 183 ISSN: 1872-7786 ISO Abbreviation: Chem. Biol. Interact. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-27 Completed Date: 2010-02-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0227276 Medline TA: Chem Biol Interact Country: Ireland |
Other Details:
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Languages: eng Pagination: 327-31 Citation Subset: IM |
Copyright Information:
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2009 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Madhav Nagar, Manipal 576104, Karnataka, India. garry_scop999@yahoo.co.in |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antihypertensive Agents / chemistry, pharmacology* Aorta, Thoracic / drug effects Calcium Channel Blockers / chemistry, pharmacology* Calcium Channels, L-Type / chemistry, metabolism* Desoxycorticosterone Endothelium, Vascular / drug effects Enzyme Inhibitors / pharmacology Glyburide / pharmacology Hypertension / chemically induced, physiopathology* Indomethacin / pharmacology Male Nitroarginine Norepinephrine / pharmacology Oxadiazoles / chemistry, pharmacology* Quinoxalines / pharmacology Rats Rats, Wistar Vasodilation / drug effects Vasodilator Agents / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; 0/4-(3-acetyl-5-(pyridine-3-yl)-2,3-dihydro-1,3,4-oxadiazole-2-yl)phenyl acetate; 0/Antihypertensive Agents; 0/Calcium Channel Blockers; 0/Calcium Channels, L-Type; 0/Enzyme Inhibitors; 0/Oxadiazoles; 0/Quinoxalines; 0/Vasodilator Agents; 10238-21-8/Glyburide; 2149-70-4/Nitroarginine; 51-41-2/Norepinephrine; 53-86-1/Indomethacin; 64-85-7/Desoxycorticosterone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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