Absence of Intrarenal ACE Protects Against Hypertension

A team of researchers, including Dr. Janos Peti-Peterdi and Dr. Alicia McDonough of the Keck School of Medicine of USC, has identified a new target for eliminating hypertension, which is a leading cause of kidney disease. The initial research was funded in part by a grant from UKRO.

The renin-angiotensin system or RAS regulates blood pressure and fluid balance in the body. If RAS becomes overactive, it can lead to consistently high blood pressure. Angiotensin-converting enzyme (ACE) and its product, angiotensin II (Ang II), play important roles in RAS. Ang II causes the blood vessels to constrict and blood pressure to rise. Many blood pressure medications, such as ACE inhibitor drugs, work by interfering with the actions of Ang II. Recently, lead researcher Dr. Romer Gonzalez-Villalobos of Cedars Sinai determined that Ang II is produced both outside the kidney in the systemic circulation and inside the kidney itself.

The new research study focuses on the renin-angiotensin system within the kidney, specifically exploring the the role of intrarenal ACE in response to hypertensive stimuli. The research team studied mice with no ACE activity in the kidneys as well as those with minimal activity. Introducing Ang II serum infusion produced full-blown hypertension in wild-type mice, but only a “blunted” hypertensive effect in altered mice, leading the scientists to conclude that the absence of ACE in the kidney protects against hypertension.

Further study showed that when intrarenal RAS is activated, kidney Ang II increases sodium and water reabsorption along the nephron, raising blood pressure. The finding highlights the specific way that intrarenal RAS can cause hypertension and paves the way for potential new hypertension treatments that could block or reduce renal ACE activity.


The Absence of Intrarenal ACE Protects Against Hypertension, Journal of Clinical Investigation, May 1, 2013



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