Intratubular, intracellular, and mitochondrial Angiotensin II/AT1a receptor/NHE3 signaling in the proximal tubules plays a critical role in maintaining basal blood pressure and the development of Ang II-induced hypertension.
Does deletion of AT1a receptors or NHE3 in proximal tubules reduce Ang II-induced hypertension in mice?
Intratubular and intracellular Ang II/AT1a receptor signaling in the proximal tubules plays a critical role in the development of Ang II-induced hypertension, highlighting a potential novel therapeutic target.
Hypertension is well recognized to be the most important risk factor for cardiovascular diseases, stroke, and end-stage kidney failure. A quarter of the world’s adult populations and 46% of the US adults develop hypertension and currently require antihypertensive treatments. Only 50% of hypertensive patients are responsive to current antihypertensive drugs, whereas remaining patients may continue to develop cardiovascular, stroke, and kidney diseases. The mechanisms underlying the poorly controlled hypertension remain incompletely understood. Recently, we have focused our efforts to uncover additional renal mechanisms, pathways, and therapeutic targets of poorly controlled hypertension and target organ injury using novel animal models or innovative experimental approaches. Specifically, we studied and elucidated the important roles of intratubular, intracellular, and mitochondrial angiotensin II (Ang II) system in the development of Ang II-dependent hypertension. The objectives of this invited article are to review and discuss our recent findings that (a) circulating and intratubular Ang II is taken up by the proximal tubules via the (AT 1 ) AT 1a receptor-dependent mechanism, (b) intracellular administration of Ang II in proximal tubule cells or adenovirus-mediated overexpression of an intracellular Ang II fusion protein selectively in the mitochonria of the proximal tubules induces blood pressure responses, and (c) genetic deletion of AT 1 (AT 1a ) receptors or the Na + /H + exchanger 3 selectively in the proximal tubules decreases basal blood pressure and attenuates Ang II-induced hypertension. These studies provide a new perspective into the important roles of the intratubular, intracellular, and mitochondrial angiotensin II/AT 1 (AT 1a ) receptor signaling in Ang II-dependent hypertensive kidney diseases.
Li et al. (Mon,) conducted a review in Hypertension and Kidney Injury. Intratubular, intracellular, and mitochondrial Angiotensin II/AT1a receptor/NHE3 signaling in the proximal tubules plays a critical role in maintaining basal blood pressure and the development of Ang II-induced hypertension.