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      The Renin-Angiotensin and Renal Dopaminergic Systems Interact in Normotensive Humans

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          The renin-angiotensin-aldosterone (RAAS) and renal dopaminergic systems interact to maintain sodium balance. High NaCl intake increases renal synthesis of dopamine and dopaminergic receptor activity, decreasing epithelial sodium transport, whereas sodium deficit activates the RAAS, increasing epithelial sodium transport. We tested the hypothesis that attenuation of the natriuretic effect of dopamine D 1-like receptors during salt restriction results in part from increased RAAS activity in seven salt-resistant normotensive adults using a double-blind placebo-controlled balanced crossover design. All subjects attained sodium balance on low (50 mmol Na +/day) and high (300 mmol Na +/day) NaCl diets, administered 4 weeks apart. Sodium, potassium, lithium, para-aminohippurate, and creatinine clearances were measured before, during, and after a 3-hour infusion of fenoldopam, a D 1-like receptor agonist, with and without pretreatment with enalapril, an angiotensin converting enzyme inhibitor. On the high NaCl diet, fenoldopam-induced natriuresis was associated with the inhibition of renal proximal and distal tubule sodium transport. On the low NaCl diet, fenoldopam decreased renal distal tubule sodium transport but did not cause natriuresis. The addition of enalapril to fenoldopam restored the natriuretic effect of fenoldopam and its inhibitory effect on proximal tubule sodium transport. Thus, on a high NaCl diet fenoldopam causes natriuresis by inhibiting renal proximal and distal tubule transport, but on a low NaCl diet the increased RAAS activity prevents the D 1-like receptor from inhibiting renal proximal tubule sodium transport, neutralizing the natriuretic effect of fenoldopam. These results demonstrate an interaction between the renin-angiotensin and renal dopaminergic systems in humans and highlight the influence of dietary NaCl on these interactions.

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          Author and article information

          J Am Soc Nephrol
          J. Am. Soc. Nephrol
          Journal of the American Society of Nephrology : JASN
          American Society of Nephrology
          January 2016
          14 May 2015
          : 27
          : 1
          : 265-279
          Departments of [* ]Pediatrics and
          []Internal Medicine, MedStar-Georgetown University Hospital, Washington, DC;
          []Department of Medicine, Division of Nephrology, and
          []Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland;
          [§ ]Clinical Research Unit, Georgetown University Medical Center, Washington, DC; and
          []Department of Internal Medicine, The University of Virginia, Charlottesville, Virginia
          Author notes
          Correspondence: Dr. Aruna R. Natarajan, Associate Professor of Pediatrics, Pharmacology, and Physiology, Department of Pediatrics, Division of Critical Care, MedStar-Georgetown University Hospital, 3800, Reservoir Road, NW, Washington DC 20007. E-mail: an5@ 123456georgetown.edu
          PMC4696568 PMC4696568 4696568 2014100958
          Copyright © 2016 by the American Society of Nephrology
          Page count
          Pages: 15
          Clinical Research
          Custom metadata
          January 2016

          natriuresis, salt, enalapril, dopamine, hypertension


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