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  • Research Summary of Yiling Fu, MD, PhD

    Hypertension is a major risk factor for many cardiovascular diseases, including stroke, coronary artery and peripheral vascular disease and chronic kidney disease. The underlying mechanisms responsible for increases in blood pressure have yet been fully elucidated. Kidneys regulate extracellular fluid volume by altering Na+ and water excretion. Inappropriate salt and water retention may lead to hypertension. Tubuloglomerular feedback (TGF) is a crucial factor of the kidney that regulates renal hemodynamics and thus affects sodium and water balances and blood pressure. It operates as a negative feedback loop, sensing changes in luminal NaCl concentration at the macula densa (MD).

    In genetic animal models of hypertension, TGF is enhanced, and resetting of TGF may also contribute to salt-sensitive hypertension in humans. NO acts as an endogenous antioxidative agent by reacting with O2- generated in the living tissues, thus it provides a protective function against the action of O2- in many organs. Attenuated NO bioavailability, being one of the important cardiovascular risk factors, has been demonstrated in patients with essential hypertension, renovascular hypertension, malignant hypertension and preeclampsia, as well as in experimental models such as Ang II-mediated hypertension, Dahl salt-sensitive hypertension, lead-induced hypertension, obesity-associated hypertension, mineralocorticoid hypertension and aldosterone-provoked hypertension. It is reported that both NO and O2- generation were enhanced by the MD during the TGF response. NO in MD blunts the TGF response; O2- generated by the MD enhances TGF by scavenging NO.

    Therefore, the NO bioavailability in the MD, mainly through the interactions between NO and O2- is a key factor that regulates the TGF response.

    The current study will be focused on the interaction between NO and O2- in the MD during TGF in physiological conditions, and whether the production of NO and O2- in the MD has any alteration in hypertension.