Renal autocrine neuropeptide FF (NPFF) signaling regulates blood pressure

Hewang Lee, Division of Renal Diseases and Hypertension, Department of Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, NW, Washington, DC, 20052, USA. lih@gwu.edu.
Bibhas Amatya, Division of Renal Diseases and Hypertension, Department of Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, NW, Washington, DC, 20052, USA.
Van Anthony Villar, Division of Renal Diseases and Hypertension, Department of Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, NW, Washington, DC, 20052, USA.
Laureano D. Asico, Division of Renal Diseases and Hypertension, Department of Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, NW, Washington, DC, 20052, USA.
Jin Kwon Jeong, Department of Pharmacology and Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC, 20052, USA.
Jun Feranil, Division of Renal Diseases and Hypertension, Department of Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, NW, Washington, DC, 20052, USA.
Shaun C. Moore, Division of Renal Diseases and Hypertension, Department of Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, NW, Washington, DC, 20052, USA.
Xiaoxu Zheng, Division of Renal Diseases and Hypertension, Department of Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, NW, Washington, DC, 20052, USA.
Michael Bishop, Division of Renal Diseases and Hypertension, Department of Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, NW, Washington, DC, 20052, USA.
Jerald P. Gomes, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Jacob Polzin, Division of Renal Diseases and Hypertension, Department of Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, NW, Washington, DC, 20052, USA.
Noah Smeriglio, Department of Chemistry, Columbian College of Arts and Sciences, The George Washington University, Washington, DC, 20052, USA.
Pedro A. de Castro, Division of Renal Diseases and Hypertension, Department of Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, NW, Washington, DC, 20052, USA.
Ines Armando, Division of Renal Diseases and Hypertension, Department of Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, NW, Washington, DC, 20052, USA.
Robin A. Felder, Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, VA, 22908.5, USA.
Ling Hao, Department of Chemistry, Columbian College of Arts and Sciences, The George Washington University, Washington, DC, 20052, USA.
Pedro A. Jose, Division of Renal Diseases and Hypertension, Department of Medicine, The George Washington University School of Medicine and Health Sciences, 2300 Eye Street, NW, Washington, DC, 20052, USA.

Document Type

Journal Article

Publication Date

7-4-2024

Journal

Scientific reports

Volume

14

Issue

1

DOI

10.1038/s41598-024-64484-9

Keywords

Blood pressure; Brain; Dopamine D1-like receptor; Kidney; Neuropeptide FF

Abstract

The kidney and brain play critical roles in the regulation of blood pressure. Neuropeptide FF (NPFF), originally isolated from the bovine brain, has been suggested to contribute to the pathogenesis of hypertension. However, the roles of NPFF and its receptors, NPFF-R1 and NPFF-R2, in the regulation of blood pressure, via the kidney, are not known. In this study, we found that the transcripts and proteins of NPFF and its receptors, NPFF-R1 and NPFF-R2, were expressed in mouse and human renal proximal tubules (RPTs). In mouse RPT cells (RPTCs), NPFF, but not RF-amide-related peptide-2 (RFRP-2), decreased the forskolin-stimulated cAMP production in a concentration- and time-dependent manner. Furthermore, dopamine D1-like receptors colocalized and co-immunoprecipitated with NPFF-R1 and NPFF-R2 in human RPTCs. The increase in cAMP production in human RPTCs caused by fenoldopam, a D1-like receptor agonist, was attenuated by NPFF, indicating an antagonistic interaction between NPFF and D1-like receptors. The renal subcapsular infusion of NPFF in C57BL/6 mice decreased renal sodium excretion and increased blood pressure. The NPFF-mediated increase in blood pressure was prevented by RF-9, an antagonist of NPFF receptors. Taken together, our findings suggest that autocrine NPFF and its receptors in the kidney regulate blood pressure, but the mechanisms remain to be determined.

Department

Medicine

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