Alicia McDonough: Intrarenal Ang II as Target to Eliminate Hypertension

Dr. Alicia McDonough of the Keck School of Medicine of USC

Dr. Alicia McDonough

A $50,000 grant from UKRO allowed a cross-town collaboration between the labs of Dr. Alicia McDonough at the Keck School of Medicine of USC and Dr. Romer Gonzalez-Villalobos of Cedars-Sinai Medical Center on the topic of how the kidney regulates blood pressure. Their paper, “The Absence of Intrarenal ACE Protects Against Hypertension,” has been published in the prestigious and high impact Journal of Clinical investigation and has sparked commentaries in JCI and NDT.

About the Initial Study

Thirty percent of the population in the United States has hypertension or high blood pressure, which is a leading cause of kidney disease. Most anti-hypertensive medications, such as ACE inhibitor drugs, work by interfering with the actions of a hormone called angiotensin II or by interfering with sodium transporters, in the case of diuretics.

Recently, Dr Gonzalez-Villalobos determined that Ang II is produced both outside the kidney in the systemic circulation and inside the kidney itself. Since Dr. McDonough has the tools to determine how Ang II works to raise blood pressure, together they asked whether the production of Ang II inside the kidney regulates blood pressure and contributes to the generation of hypertension. Dr. Gonzalez-Villalobos had already created a unique genetic mouse model that had normal systemic levels of Ang II, but lacked the machinery to make Ang II in the kidney (ACE10/10). He found that when mice were treated with Ang II, blood pressure increased less in the ACE10/10 mice than in unaltered mice, specifically because in normal mice, systemic Ang II stimulates the production of kidney Ang II and this pathway was eliminated in the ACE10/10. The McDonough lab took kidneys from these mice and examined every sodium transporter to determine why the blood pressure was lower in ACE 10/10. They discovered that three main diuretic targets were reduced in the ACE10/10, as well as a key regulator. This finding provides the opportunity for clinicians and scientists to think in new ways about how to eliminate hypertension and eradicate kidney disease by targeting the intra-kidney production of Ang II.

Read more about the research in our blog.

 

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