Abstract
Ischemia/reperfusion (I/R) in post-arterior post-capillary venules induces an acute inflammatory response, characterized by increased adherence and emigration of leukocytes and vascular permeability, all of which play important roles in cardiovascular disease. The aim of this study was to determine the roles of angiotensin II and AT&sub1; receptor blockade in microvascular I/R injury in rats. Rats were anesthetized and intubated, then the peritoneum was opened and the mesentery was revailed. Small post-capillary venules were examined by in vivo fluorescence microscopy. The flow of erythrocytes and leukocytes was observed under the microscope and video recorded for later dynamic analyses. The superior mesenteric artery (SMA) was ligated with polyethylene tubing and released to induce I/R (20 min of ischemia/60 min of reperfusion). Subsequently, leukocyte adhesion, emigration and albumin leakage were compared with those of non-I/R controls. I/R injury was significantly suppressed by superfusing tissues with the AT&sub1; receptor antagonist losartan (LO; 10μM). The beneficial effects of LO were inhibited by topical application of either the bradykinin B&sub2; receptor antagonist HOE140 (10 nM) or nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME 10μM). The effects of LO were lost in the presence of AT&sub2; receptor blocker PD 123319 (PD).
In conclusion, LO suppressed and protected against I/R injuries. The possible interaction between AT&sub1; and AT&sub2; receptors was also suggested.
