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Geraniin is a diuretic by inhibiting the Na+-K+-2Cl- cotransporter NKCC2.

Erika MorenoJuan A GayossoJosé R MontejanoGeorgina AlmaguerNorma VázquezCristino CruzAdriana MercadoNorma A BobadillaGerardo GambaAlfredo SierraVictoria Ramirez-Gonzalez
Published in: American journal of physiology. Renal physiology (2017)
Geranium seemannii Peyr is a perennial plant endemic to central Mexico that has been widely used for its diuretic effect, but the responsible compound of this effect is unknown as well as the mechanism by which the diuretic effect is achieved. Geraniin is one of the compounds isolated from this kind of geranium. This study was designed to determinate whether geraniin possesses diuretic activity and to elucidate the mechanism of action. Geraniin was extracted and purified from Geranium seemannii Peyr. Male Wistar rats were divided into four groups: 1) Control, 2) 75 mg/kg of geraniin, 3) 20 mg/kg of furosemide, and 4) 10 mg/kg of hydrochlorothiazide. Each treatment was administered by gavage every 24 h for 7 days. The urinary excretion of electrolytes and the fractional excretion of sodium (FENa) were determined. To uncover the molecular target of geraniin, Xenopus laevis oocytes were microinjected with cRNAs encoding the Na+-Cl- cotransporter (NCC) and the Na+-K+-2Cl- cotransporter NKCC2 to functionally express these cotransporters. Geraniin significantly increased diuresis, natriuresis, and calciuresis to a similar extent as was observed in the furosemide-treated rats. Consistent with the furosemide-like effect, in X. laevis oocytes, geraniin significantly reduced the activity of NKCC2, with no effect on NCC activity. In contrast to furosemide, the effect of geraniin on NKCC2 was irreversible, apparently due to its inhibitory effect on heat shock protein 90. Our observations suggest that geraniin could have a potential role in the treatment of hypertension or edematous states.
Keyphrases
  • blood pressure
  • heat shock protein
  • magnetic resonance imaging
  • magnetic resonance
  • computed tomography
  • acute heart failure
  • combination therapy