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

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.

• Authors: Yogendra Singh, Kulwinder Singh, P L Sharma
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 373 Issue 1-2 Pg. 189-94 (Jan 2013) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 23108791 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AVE 0991
• Amides
• Antihypertensive Agents
• Fumarates
• Imidazoles
• Proto-Oncogene Mas
• Proto-Oncogene Proteins
• Receptors, G-Protein-Coupled
• Desoxycorticosterone
• aliskiren
• Renin

Topics

• Amides (administration & dosage)
• Animals
• Antihypertensive Agents (administration & dosage)
• Blood Pressure (drug effects)
• Desoxycorticosterone
• Dose-Response Relationship, Drug
• Drug Synergism
• Drug Therapy, Combination
• Female
• Fumarates (administration & dosage)
• Hypertension (chemically induced, drug therapy, physiopathology)
• Imidazoles (administration & dosage)
• Male
• Proto-Oncogene Mas
• Proto-Oncogene Proteins (agonists)
• Rats
• Rats, Wistar
• Receptors, G-Protein-Coupled (agonists)
• Renin (antagonists & inhibitors)