Effect of Ramipril, Valsartan, Candesartan and Lacidipine on inflammation and gastric ulcer in rats

ABSTRACT

The present study investigated and compared the effect of the angiotensin converting enzyme inhibitor ramipril and the angiotensin II receptor blockers valsartan and candesartan and the calcium channel blocker lacidipine on inflammation and gastric ulcer in rats. The acute inflammation was induced by intraplantar injection of carrageenan [1%] in the rat hind paw. Gastric ulcer was evoked by s.c. indomethacin [20 mg/kg]. When given s.c. 30 min prior to induction of inflammation, ramipril [0.23 and 0.45 mg/kg], valsartan [7.5 and 15 mg/kg], candesartan [0.72 and 1.44 gm/kg] failed to reduce paw oedema response. Meanwhile, lacidipine at the lower dose of 0.18 mg/kg displayed mild anti-inflammatory activity up to 1 hr, reducing paw odema by 26.7% for 1 hr post-carrageenan, while a higher dose of 0.36 mg/kg inhibited oedema formation by 33.5, 31, 23.6 and 22.3% at 1, 2, 3 and 4 hr post-carrageenan, respectively. The acute gastric mucosal lesions evoked by indomethacin in the rat were aggravated by co-administration of ramipril 0.23 and 0.45 mg/kg, valsartan 7.5 and 15 mg/kg, lacidipne 0.18 and 0.36 mg/kg and candesartan 0.72 mg/kg, but reduced by candesartan 1.44 mg/kg. Findings in the present study do not favor an anti-inflammatory activity for ramipril, valsartan and candesartan, but indicates an antioedema effect for lacidipine at the doses employed. These agents are likely to adversely affect gastric mucosal integrity and enhance the indomethacin-induced gastric injury