The effect of angiotensin II on the expression of inos and COX-2 in rat stomach exposed to ischemia-reperfusion

Renin-Angiotensin system (RAS) is the most important regulatory system in vascular homeostasis. Angiotensin II (Ang II) which is the most effective member of RAS, is defined as a growth factor that has an active role on cardiovascular and renal diseases. At last decade, it is revealed that Ang II has a key role in development of inflammatory response. Experimental ischemia-reperfusion (I/R) model which triggers inflammatory response that depends on ischemia and reperfusion duration is an effective model. In this study, we aimed to clarify the effect of Ang II on expression of iNOS and COX-2 enzymes which are related to inflammatory response in rat stomach which is exposed to ischemia-reperfusion. According to our purpose, control, I/R, I/R+Candesartan, I/R + PD123319, I/R + Captopril groups were designed. 30 min ischemia, subsequent 24 hrs reperfusion was applicated at I/R group. AT1 RB; Candesartan (1 mg/kg/day), AT2 RB; PD123319 (3 mg/kg/day) or ACE inhibitor Captopril (20 mg/kg/day) were given twice a day for five days. After that, I/R procedure was applicated. Myeloperoxidase (MPO) activity, PGE2 and NOx (nitrate+nitrite) quantities and expressions of iNOS and COX-2 were assayed in gastric tissues. Ang II level was measured in plasma. After 30 min ischemia duration subsequently 24 hrs reperfusion period, MPO activity was increased. This increment was abolished with candesartan. PGE2 quantity decreased, but there were no changes statisticaly significant and NOx quantities in I/R group. The expression of COX-2 was increased in I/R+PD123319 and I/R+Candesartan groups.The increment of iNOS expression was suppressed with Candesartan although NOx quantity was not changed related to I/R. There was no statistically significance in plasma Ang II level between all the groups. In conclusion; Angiotensin II may be responsible for increase of iNOS expression which is related to I/R, via AT1 receptor pathway. Key words: Ischemia and reperfusion, Ang II, iNOS, COX-2, candesartan, PD123319, captopril, inflammation.