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Human natriuretic hormones, xanthurenic acid 8‐O‐β‐D‐glucoside and xanthurenic acid 8‐O‐sulfate, new potent natriuretic and non‐kaliuretic tryptophan derivatives
Author(s) -
Cain Christopher D.,
Shankel Stewart W.,
Schroeder Frank C.,
Mitchnick Mark,
Schmertzler Michael,
Bricker Neal S.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.943.2
Subject(s) - natriuresis , kaliuresis , xanthurenic acid , medicine , acetazolamide , chemistry , endocrinology , hormone , pharmacology , excretion , biochemistry , tryptophan , amino acid
For decades, researchers have searched for a non‐peptidic natriuretic hormone that acts as a definitive modulator of renal sodium excretion. We present herein the demonstration of natriuretic activity of two such recently identified and synthesized molecules isolated from human urine (PNAS Nov. 6, 2007 104: 17873–17878). These molecules are xanthurenic acid 8‐O‐β‐D‐glucoside (termed “NH”) and xanthurenic acid 8‐O‐sulfate (termed “NH‐1”). Substantial natriuresis occurred in rats following administration of synthesized NH and NH‐1 administered intravenously, intra‐arterially, and orally. With the first two routes, natriuresis began during or shortly after the infusion and persisted for one to two hours. Kaliuresis was small or non‐existent. With oral administration, natriuresis was delayed in onset but generally prolonged. When acetazolamide was infused along with the natriuretic hormones, natriuresis was enhanced, but the typical acetazolamide‐induced kaliuresis was blocked. We believe that these two natriuretic compounds may represent a new class of hormone and could have important therapeutic uses in the diagnosis and/or treatment of hypertension and fluid disorders. This research was funded by Naturon Pharmaceutical Corporation.