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 |
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| Authors: | Girish R Bankar Gopalan Kutty Nampurath Pawan G Nayak Shoumyo Bhattacharya |
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| Institution: | 1. Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Madhav Nagar, Manipal 576104, Karnataka, India;2. Department of Pharmacognosy, Manipal College of Pharmaceutical Sciences, Manipal University, Madhav Nagar, Manipal 576104, Karnataka, India;1. CPEPA, Department of Chemistry, Karnatak University, Dharwad 580003, Karnataka, India;2. CPEPA, Department of Physics, Karnatak University, Dharwad 580003, Karnataka, India;1. Department of Chemistry, Government College University, Lahore 54000, Pakistan;2. H E J Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;3. Department of Biochemistry, University of Agriculture, Faisalabad 38040, Pakistan;4. Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan;5. Department of Biochemistry, Abdul Wali Khan University, Mardan 23200, Pakistan;6. Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia;1. College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, PR China;2. School of Science and Technology, Zhejiang International Studies University, Hangzhou, Zhejiang 310012, PR China;1. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia;2. Faculty of Applied Science Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor, Malaysia;3. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;1. Department of Chemistry, Hazara University, Mansehra 21300, Pakistan;2. Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia;3. Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan;4. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia;5. Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D.E., Malaysia;6. Department of Neuroscience Research, Institute of Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia;7. Department of Conservation Sciences, Hazara University, Mansehra 21300, Pakistan;8. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan |
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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 ± 4.1 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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