Author's Department

OTHER (include in Notes to Administrator)

Date Submitted


Research Mentor and Department

Dr. Babu Padanilam, Department of Cellular and Integrative Physiology at University of Nebraska Medical Center




Renal denervation before ischemic injury has been shown to protect against fibrogenesis and the inflammatory response, which are two causes for the progression of chronic kidney disease. However, the administration of norepinephrine (NE) to denervated renal systems induced fibrogenesis and inflammation after ischemic injury. Our previous data indicates that NE-mediated stimulation of the α2-AR receptors is responsible for regulating several of the processes implicated in fibrogenesis and inflammation, including the accumulation, migration, and infiltration of macrophages to the site of injury; this is especially relevant as macrophages have been implicated as one potential cause for the inflammatory response.

Recent studies, completed in response to the idea that stimulation with clonidine or moxonidine seems to protect against renal fibrogenesis, suggest that NE-mediated stimulation of the α2-AR receptors is responsible for fibrogenesis and inflammation. This is supported by the fact that moxonidine inhibits the release of norepinephrine while simultaneously stimulating the central α2- AR receptors while clonidine is responsible for preventing the release of renin which, as explained by the renin- angiotensin-aldosterone system, prevents the release of norepinephrine from sympathetic nerve endings and the inhibition of its re-uptake. However, there are few studies that explain how the absence of norepinephrine could affect macrophage function.

To define the role that norepinephrine plays in renal fibrogenesis and the inflammatory response after ischemia, three experiments were performed to answer the following questions: 1. Can treating the macrophage cell cultures with LPS induce differentiation between M1 and M2 macrophage phenotypes? 2. Do injured macrophages have the capacity to release norepinephrine? and 3.If so, what is the effect of varying concentrations of norepinephrine on the differentiation between M1 and M2 macrophage phenotypes?