Kidney Mass Reduction Leads to l-Arginine Metabolism-Dependent Blood Pressure Increase in Mice.

Abstract

BACKGROUND:

Uninephrectomy (UNX) is performed for various reasons, including kidney cancer or donation. Kidneys being the main site of l-arginine production in the body, we tested whether UNX mediated kidney mass reduction impacts l-arginine metabolism and thereby nitric oxide production and blood pressure regulation in mice.

METHODS AND RESULTS:

In a first series of experiments, we observed a significant increase in arterial blood pressure 8 days post-UNX in female and not in male mice. Further experimental series were performed in female mice, and the blood pressure increase was confirmed by telemetry. l-citrulline, that is used in the kidney to produce l-arginine, was elevated post-UNX as was also asymmetric dimethylarginine, an inhibitor of nitric oxide synthase that competes with l-arginine and is a marker for renal failure. Interestingly, the UNX-induced blood pressure increase was prevented by supplementation of the diet with 5% of the l-arginine precursor, l-citrulline. Because l-arginine is metabolized in the kidney and other peripheral tissues by arginase-2, we tested whether the lack of this metabolic pathway also compensates for decreased l-arginine production in the kidney and/or for local nitric oxide synthase inhibition and consecutive blood pressure increase. Indeed, upon uninephrectomy, arginase-2 knockout mice (Arg-2-/-) neither displayed an increase in asymmetric dimethylarginine and l-citrulline plasma levels nor a significant increase in blood pressure.

CONCLUSIONS:

UNX leads to a small increase in blood pressure that is prevented by l-citrulline supplementation or arginase deficiency, 2 measures that appear to compensate for the impact of kidney mass reduction on l-arginine metabolism.

• Authors: Samyuktha Muralidharan Pillai, Petra Seebeck, Ralph Fingerhut, Ji Huang, Xiu-Fen Ming, Zhihong Yang, François Verrey
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 7 Issue 5 (02 25 2018) ISSN: 2047-9980 [Electronic] England
• PMID: 29478971 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Chemical References

• Citrulline
• Nitric Oxide
• N,N-dimethylarginine
• Arginine
• Arg2 protein, mouse
• Arginase

Topics

• Animals
• Arginase (genetics, metabolism)
• Arginine (analogs & derivatives, blood, metabolism)
• Blood Pressure (drug effects)
• Citrulline (administration & dosage, blood)
• Female
• Kidney (metabolism, pathology, surgery)
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Nephrectomy (adverse effects)
• Nitric Oxide (metabolism)
• Organ Size