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Last Updated: Sep 15, 2017 - 4:49:58 AM
Research Article
Nephrology Channel

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Latest Research : Nephrology

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Mouse model shows that kidney-specific dopamine system important for kidney function and blood pressure regulation

Jul 19, 2011 - 6:19:38 PM , Reviewed by: Dr. Sanjukta Acharya

"These animals retain salt and water when they don't have sufficient dopamine production in the kidney," said Raymond Harris, M.D., chief of the Division of Nephrology and Hypertension at Vanderbilt. "Our studies highlight this whole other hormonal system that appears to balance or put the brakes on the renin-angiotensin system."


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[RxPG] Vanderbilt University Medical Center investigators have demonstrated that dopamine produced outside the brain – in the kidneys – is important for renal function, blood pressure regulation and life span. Their studies, published in the July Journal of Clinical Investigation, suggest that the kidney-specific dopamine system may be a therapeutic target for treating hypertension and kidney diseases such as diabetic nephropathy.

Previous studies had suggested a role for dopamine in regulating kidney function and total body fluid volume, "but how that mechanism works was not clear," said Raymond Harris, M.D., chief of the Division of Nephrology and Hypertension at Vanderbilt.

To explore dopamine's role in the kidney, Harris and Ming-Zhi Zhang, M.D., assistant professor of Medicine at Vanderbilt, eliminated kidney-specific dopamine production in mice (by knocking out a dopamine-generating enzyme only in the kidney) and studied the outcome.

They found that mice lacking kidney dopamine had high blood pressure at baseline and became more hypertensive when they consumed a high-salt diet, suggesting they may be a good model of salt-sensitive (essential) hypertension, Harris said. Alterations in the kidney dopamine system may predispose individuals to hypertension, he noted.

The investigators also showed that elimination of kidney dopamine increased renin production, which activates the angiotensin II system to increase salt and water reabsorption – and produce hypertension.

"These animals retain salt and water when they don't have sufficient dopamine production in the kidney," Harris said. "Our studies highlight this whole other hormonal system that appears to balance or put the brakes on the renin-angiotensin system."

Currently, the renin-angiotensin system is the major target for treating chronic kidney diseases. Discovering another target – the kidney dopamine system – is exciting, the researchers said. They are exploring whether specific drugs that enhance the kidney dopamine system are effective in blocking hypertension and treating progressive kidney diseases.

The investigators predicted changes in kidney function in the mouse model, but they were "very surprised" to discover that the modified mice only lived about half as long as normal mice (15 months versus 30 months). They found increases in stress-related proteins in the kidney, heart and vasculature, suggesting that elimination of kidney dopamine causes systemic effects, Harris said.

"This kidney-specific dopamine system is not only important for kidney function and blood pressure regulation, but also for the overall health of the animal," Harris said. "If the dopamine system in the kidney is altered, the animals have a markedly shortened life span."




Publication: Journal of Clinical Investigation- July 2011 issue

Funding information and declaration of competing interests: The research was supported by the National Institutes of Health, the Vanderbilt O'Brien Center and by the Veterans Administration. Harris is the Ann and Roscoe R. Robinson Professor of Nephrology.
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 About Dr. Sanjukta Acharya
This news story has been reviewed by Dr. Sanjukta Acharya before its publication on RxPG News website. Dr. Sanjukta Acharya, MBBS MRCP is the chief editor for RxPG News website. She oversees all the medical news submissions and manages the medicine section of the website. She has a special interest in nephrology. She can be reached for corrections and feedback at sanjukta.acharya@rxpgnews.com
RxPG News is committed to promotion and implementation of Evidence Based Medical Journalism in all channels of mass media including internet.
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