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

• Published in: Journal of the American Society of Nephrology 2016-01, Vol.27 (1), p.265-279
• Main Authors: Natarajan, Aruna R, Eisner, Gilbert M, Armando, Ines, Browning, Shaunagh, Pezzullo, John C, Rhee, Lauren, Dajani, Mustafa, Carey, Robert M, Jose, Pedro A
• Format: Article
• Language: English
• Subjects: Adult; Blood Pressure - physiology; Clinical Research; Cross-Over Studies; Diet, Sodium-Restricted; Double-Blind Method; Female; Humans; Kidney - metabolism; Male; Receptors, Dopamine - physiology; Renin-Angiotensin System - physiology
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2014100958

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 D1-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 D1-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 D1-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.