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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 NG-nitro-l-arginine hypertensive rats

Bankar, Girish R and Nampurath, Gopalan Kutty and Nayak, Pawan G and Bhattacharya, Shoumyo (2010) 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 NG-nitro-l-arginine hypertensive rats. Chemico-Biological Interactions, 183 (2). pp. 327-331. ISSN 0009-2797

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Abstract

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 NG-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±4.1mmHg, whereas after administration of NOX-1 to hypertensive rats, MSBB was 127.8±4.5 and 120.2±5.1mmHg, 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. NEinduced 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

Item Type: Article
Uncontrolled Keywords: DOCA salt-induced hypertension; L-NNA-induced hypertension; Endothelial dysfunction; Aortic rings; 1,3,4-Oxadiazole
Subjects: Pharmacy > MCOPS Manipal > Pharmacognosy
Pharmacy > MCOPS Manipal > Pharmacology
Depositing User: KMC Manipal
Date Deposited: 27 Jan 2012 10:43
Last Modified: 27 Jan 2012 10:43
URI: http://eprints.manipal.edu/id/eprint/2732

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