UNIVERISTY OF MISSISSIPPI MEDICAL CENTER
Grant: $124,922 - National Institutes of Health - Aug. 18, 2009
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Award Description: The prevailing paradigm regarding the relationship of angiotensin II (AngII) and renal injury is that AngII is uniformly injurious to the kidney. Our recent studies have found that a chronic infusion of subpressor doses of AngII (SP-AngII) has an unexpected duality of effects: on the one hand it is a fundamental catalyst of chronic renal injury; on the other, it protects against acute renal injury (resembling ischemic preconditioning). Because these effects are associated with induction of MCP-1 (a pro-inflammatory chemokine implicated in renal and vascular injury) and HO-1 (a heme-degrading enzyme with vasorelaxant, antioxidant and anti-inflammatory properties), we hypothesized that SP-AngII-induced MCP-1 instigates injury, whereas HO-1 mitigates injury and procures resistance against ARF. This proposed supplement will focus on accelerating the progress of Specific Aim 2 of the parent grant that tests the following hypothesis: Sp-AngII-induced MCP-1 is a major determinant of chronic renal injury, whereas the concomitant induction of HO-1 lessens the deleterious effects of SP-AngII-induced MCP-1. We will manipulate the expression and/or activity of MCP-1 and HO-1 to determine their role in SP-AngII-induced HTN and renal injury. We then examine how salt interacts with these factors.
Project Description: Dr. Julio Pedro Juncos was recently hired and is just starting his experiments. Funding for these experiments up until now have been independent from the ARRA Supplement funds so 0% of the budget has been used. We recently found that female rats have increased HO-1 during acute kidney injury compared to males. This may explain in part why females suffer less renal injury than males. We are starting experiments in which we determine whether estrogen-induced increases in HO-1 contribute to the decreased renal injury observed during AngII in females.
Jobs Summary: no jobs created (Total jobs reported: 0)
Project Status: Less Than 50% Completed
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