Role of angiotensin II in experimental Venezuelan equine encephalitis in rats.

Venezuelan equine encephalitis (VEE) is a viral disease transmitted by mosquitoes. The inflammation induced by the VEE virus is associated with a high mortality rate in mice. Angiotensin II (Ang II), a pro-inflammatory molecule, is produced in the normal rat brain. There is no information about the role of this molecule in the inflammatory events occurring during VEE and the effect of inflammation on the mortality rate in VEE-virus-infected rats. This study was designed to determine the role of Ang II in VEE and to analyze the effect of inflammation on mortality in infected rats. Two groups of rats were studied: 1) Virus-infected animals and controls (n = 60) were treated with losartan (a blocker of the Ang II-AT1 receptor) or with pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB) or left untreated and analyzed for morbidity and mortality. 2) Animals treated using the same protocol (n = 30) were sacrificed at day 4 postinfection and analyzed by immunohistochemistry and histopathology and for cytokine production. Increased expression of Ang II, ICAM-1, ED-1 and cytokines (IL-1α, MCP-1, IL-6 and IL-10) in infected animals was observed. The main histopathology findings were dilated capillaries and capillaries with endothelial detachment. Losartan and PDTC reduced the expression of IL-1α, MCP-1, and IL-10, and the number of dilated capillaries and capillaries with endothelial detachment. Survival analysis showed that 100% mortality was reached earlier in infected rats treated with losartan (day 14) or PDTC (day 11) than in untreated animals (day 19). These findings suggest that Ang II plays a role in VEE and that brain inflammation is protective against viral infection.