Document Detail

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.
MedLine Citation:
PMID:  19912999     Owner:  NLM     Status:  MEDLINE    
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.
Girish R Bankar; Gopalan Kutty Nampurath; Pawan G Nayak; Shoumyo Bhattacharya
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-11
Journal Detail:
Title:  Chemico-biological interactions     Volume:  183     ISSN:  1872-7786     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-27     Completed Date:  2010-02-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  327-31     Citation Subset:  IM    
Copyright Information:
2009 Elsevier Ireland Ltd. All rights reserved.
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Madhav Nagar, Manipal 576104, Karnataka, India.
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MeSH Terms
Antihypertensive Agents / chemistry,  pharmacology*
Aorta, Thoracic / drug effects
Calcium Channel Blockers / chemistry,  pharmacology*
Calcium Channels, L-Type / chemistry,  metabolism*
Endothelium, Vascular / drug effects
Enzyme Inhibitors / pharmacology
Glyburide / pharmacology
Hypertension / chemically induced,  physiopathology*
Indomethacin / pharmacology
Norepinephrine / pharmacology
Oxadiazoles / chemistry,  pharmacology*
Quinoxalines / pharmacology
Rats, Wistar
Vasodilation / drug effects
Vasodilator Agents / pharmacology*
Reg. No./Substance:
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

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