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  • Research Summary of Yan Lu, MD

    Kidney plays a crucial role in the regulation of long-term blood pressure and in the development of hypertension. Tubuloglomerular feedback (TGF) is an important mechanism regulates renal hemodynamic and NaCl excretion. MD senses increased NaCl delivery mediated TGF response which constricts afferent arterioles (Af-Art), reduces GFR, and restores flow in the distal nephron. If increased NaCl delivery to the MD, the TGF response will reset to permit elevation of GFR and facilitate NaCl excretion. The mechanism for the TGF resetting is unclear.

    The balance between nitric oxide (NO) and superoxide (O2-) may play an important role in TGF resetting. NO derived from MD neuronal NO synthase (nNOS) blunts TGF, whereas MD-derived O2- enhances TGF. Even though the role of MD-derived NO in the MD in modulating TGF has been established, but the net effect of this mechanism on NaCl homeostasis, renal function and blood pressure is not know.

    In addition, Ang II is a key regulator of TGF and is also important in the regulation of NaCl retention renal function and blood pressure. To test the contribution of MD-derived NO in TGF resetting in Ang II induced hypertension, we will delete MD nNOS to lower MD-derived NO. We have developed novel tissue specific knockout mouse model (NKCC2-nNOSKO) in which all splice variants of nNOS on the MD have been deleted by crossing NKCC2 cre mice with nNOS flox/flox mice.

    We will use microperfusion of the juxtaglomerular apparatus (JGA) in vitro level and micropuncture to measure TGF and single nephron GFR, and also measure whole kidney GFR in vivo level.  In addition, we will use telemetry to measure main arterial pressure (MAP) and measure plasma creatinine, Kidney Injury Marker (KIM-1) for renal injury analysis.