NPFF (100 nM) decreased Na+-binding lifetime from 3.52 to 3.44 nanoseconds in human renal cells, and NPFFR2 agonist infusion (20 mg/kg/day) elevated systolic blood pressure in mice.
Does Neuropeptide FF modulate renal sodium transport and blood pressure via Na+/K+-ATPase and SGLT2 in renal proximal tubules?
NPFF increases blood pressure and decreases sodium excretion by upregulating Na+/K+-ATPase and SGLT2 in the renal proximal tubule, highlighting a potential mechanism in hypertension.
Sodium homeostasis plays a critical role in managing arterial blood pressure, where an increase in renal Na + transport would lead to the development of hypertension. Neuropeptide FF (NPFF) and its two receptors, NPFFR1 and NPFFR2, are found to be expressed in various segments of the nephron such as the renal proximal tubule (RPT) and increase blood pressure (BP). However, the mechanisms by which renal NPFF is involved in raising BP are not fully understood. In human RPT cells (hRPTCs), NPFF (100 nM, 10 min) decreased the lifetime of Na + -binding (τ2) Asante NaTRIUM Green-2 from 3.52 to 3.44 nanoseconds, determined by fluorescence lifetime imaging microscopy, suggesting that NPFF increased Na + transport out of the RPT cells. Notably, in hRPTCs, NPFF increased the protein expressions of Na + /K + -ATPase and sodium-glucose cotransporter 2 (SGLT2) in a time- and concentration-dependent manner. Moreover, the renal-selective infusion of NPFF or NPFFR2 agonist, AC263093 (20 mg/kg/day, 7 days), causes an elevation in systolic BP. By contrast, the renal-selective infusion of RF9, an NPFFR antagonist, or silencing NPFFR1 or NPFFR2 with their siRNAs, decreased the systolic BP of C57Bl/6 mice fed a high-salt diet (4% NaCl). NPFF reduced sodium excretion and Npffr2 but not Npffr1 siRNA slightly decreased renal Na + /K + -ATPase and SGLT2 expression, while NHE3 expression was unchanged. We conclude that renal NPFFR increases BP and decreases sodium excretion that may be related to an NPFFR2-mediated upregulation of Na + /K + -ATPase and SGLT2 protein expressions in the RPT. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Qaddumi et al. (Fri,) conducted a other in Hypertension. NPFF or NPFFR2 agonist (AC263093) vs. NPFFR antagonist (RF9) or siRNAs was evaluated on Systolic blood pressure, sodium excretion, and Na+/K+-ATPase/SGLT2 protein expressions. NPFF (100 nM) decreased Na+-binding lifetime from 3.52 to 3.44 nanoseconds in human renal cells, and NPFFR2 agonist infusion (20 mg/kg/day) elevated systolic blood pressure in mice.