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Effect of combination of renin inhibitor and Mas-receptor agonist in DOCA–salt-induced hypertension in rats

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Abstract

To investigate the combined effect of aliskiren, a renin inhibitor, and AVE 0991, a Mas-receptor agonist, in experimental hypertension (HT) in rats. HT was produced by administration of deoxycorticosterone acetate (DOCA) and mean arterial blood pressure (MABP) was assessed by tail-cuff method. Treatments were started from 4th week onwards and were continued for 9 days. A significant increase in MABP was noted after 1 week in DOCA control rats, as compared with the base line value. A stable HT developed after 4 weeks of DOCA administration. Treatments with aliskiren and AVE 0991 alone, dose-dependently decreased MABP in DOCA-treated rats. Further, combination of low doses of aliskiren and AVE 0991 significantly reduced MABP, as compared with DOCA control rats and with either drug alone in low doses. It may be concluded that treatment with aliskiren produced down-regulation of both harmful Ang II–AT1-receptor and survival Ang(1–7)/Mas-receptor axis of RAAS. Treatment with combination of low doses of aliskiren and AVE 0991, for the first time, has been shown to produce synergistic blood pressure lowering effect. Therefore, combination of renin inhibitor with Mas-receptor agonist may prove beneficial for the treatment of hypertensive patients.

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Acknowledgments

This study was supported partially by a Research Grant obtained from All India Council for Technical Education, New Delhi (File no. 8023/BOR/RID/RPS-167/2007–2008). This paper is dedicated to the fond memories of Prof. Manjeet Singh who expired on 30-03-2009 while this study was in progress. We wish to express our gratitude to Sanofi-Aventis, Germany and Novartis; USA for providing AVE0991 and ALK as an ex-gratia, respectively. We also wish to our sincere thank to the management of ISF college of pharmacy for providing research facility.

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Authors and Affiliations

  1. Department of Pharmacology, ISF College of Pharmacy, Moga, 142 001, Punjab, India

    Yogendra Singh & P. L. Sharma

  2. University Institute of Pharmacy, Baba Farid University of Health Sciences, Faridkot, 151 203, Punjab, India

    Kulwinder Singh

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  1. Yogendra Singh
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  2. Kulwinder Singh
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Correspondence to Kulwinder Singh.

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Singh, Y., Singh, K. & Sharma, P.L. Effect of combination of renin inhibitor and Mas-receptor agonist in DOCA–salt-induced hypertension in rats. Mol Cell Biochem 373, 189–194 (2013). https://doi.org/10.1007/s11010-012-1489-2

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