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Angiotensin II and AT1a Receptors in the Proximal Tubules of the Kidney: New Roles in Blood Pressure Control and Hypertension.
Leite, Ana Paula de Oliveira; Li, Xiao C; Nwia, Sarah M; Hassan, Rumana; Zhuo, Jia L.
  • Leite APO; Tulane Hypertension and Renal Center of Excellence, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
  • Li XC; Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
  • Nwia SM; Tulane Hypertension and Renal Center of Excellence, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
  • Hassan R; Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
  • Zhuo JL; Tulane Hypertension and Renal Center of Excellence, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Int J Mol Sci ; 23(5)2022 Feb 22.
Article in English | MEDLINE | ID: covidwho-1736940
ABSTRACT
Contrary to public perception, hypertension remains one of the most important public health problems in the United States, affecting 46% of adults with increased risk for heart attack, stroke, and kidney diseases. The mechanisms underlying poorly controlled hypertension remain incompletely understood. Recent development in the Cre/LoxP approach to study gain or loss of function of a particular gene has significantly helped advance our new insights into the role of proximal tubule angiotensin II (Ang II) and its AT1 (AT1a) receptors in basal blood pressure control and the development of Ang II-induced hypertension. This novel approach has provided us and others with an important tool to generate novel mouse models with proximal tubule-specific loss (deletion) or gain of the function (overexpression). The objective of this invited review article is to review and discuss recent findings using novel genetically modifying proximal tubule-specific mouse models. These new studies have consistently demonstrated that deletion of AT1 (AT1a) receptors or its direct downstream target Na+/H+ exchanger 3 (NHE3) selectively in the proximal tubules of the kidney lowers basal blood pressure, increases the pressure-natriuresis response, and induces natriuretic responses, whereas overexpression of an intracellular Ang II fusion protein or AT1 (AT1a) receptors selectively in the proximal tubules increases proximal tubule Na+ reabsorption, impairs the pressure-natriuresis response, and elevates blood pressure. Furthermore, the development of Ang II-induced hypertension by systemic Ang II infusion or by proximal tubule-specific overexpression of an intracellular Ang II fusion protein was attenuated in mutant mice with proximal tubule-specific deletion of AT1 (AT1a) receptors or NHE3. Thus, these recent studies provide evidence for and new insights into the important roles of intratubular Ang II via AT1 (AT1a) receptors and NHE3 in the proximal tubules in maintaining basal blood pressure homeostasis and the development of Ang II-induced hypertension.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Angiotensin II / Receptor, Angiotensin, Type 1 / Hypertension Type of study: Experimental Studies / Prognostic study Limits: Animals / Humans Language: English Year: 2022 Document Type: Article Affiliation country: Ijms23052402

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Angiotensin II / Receptor, Angiotensin, Type 1 / Hypertension Type of study: Experimental Studies / Prognostic study Limits: Animals / Humans Language: English Year: 2022 Document Type: Article Affiliation country: Ijms23052402