Rakesh B. Patel, Kanaiyalal D. Prajapati, Bhavin M. Sonara, Manoranjan M. Sharma, Vishwanath D. Pawar, Mukul R. Jain

Abstract

The renin‐angiotensin system is involved in pathogenesis and progression of inflammatory responses. In present study, we investigated the anti-cytokine and anti-hyperalgesic potential of aliskiren in LPS (lipopolysaccharide) and CFA (complete Freund’s adjuvant) induced inflammation in rodents. After aliskiren treatment, plasma cytokines (TNF-
, IL-6) and plasma renin activity (PRA) were estimated in LPS treated mice. In CFA induced inflammatory pain model, rats were treated with aliskiren and thermal hyperalgesia was evaluated and TNF-
and IL-6 were estimated in paw. In LPS treated ICR mice, elevated TNF-
and IL-6 levels and PRA were attenuated by aliskiren. In LPS treated double transgenic mice (dTG), harboring human renin and human angiotensinogen and C57BL/6J mice, elevated TNF-
level was inhibited by aliskiren. Moreover after LPS treatment, TNF-
level was high (2.16 fold) in dTG mice than C57BL/6J. These data indicates that renin overexpression system in dTG mice is responsible for higher TNF-
level suggests role of renin in inflammation. Moreover, Aliskiren showed anti-hyperalgesic activity in CFA induced inflammatory hyperalgesia in rats, which might be due to inhibition TNF-
and IL- 6 levels, suggests the role of local renin in inflammation. Our results indicate the role of renin in experimental inflammation which is inhibited by aliskiren.