Structure-activity relationships for the hypertensinogenic activity of ouabain: Role of the sugar and lactone ring

Paolo Manunta, Bruce P. Hamilton, John M. Hamlyn

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Elevated levels of an endogenous ouabain circulate in many patients with essential hypertension. However, in contrast to ouabain, digoxin does not induce hypertension. This study investigated the hypothesis that within a single cardiac glycoside, the structural elements that induce hypertension differ from those responsible for high potency as a sodium pump inhibitor. Normal male Sprague-Dawley rats received infusions of vehicle (VEH), rhamnose (RHA), ouabain (OUA), ouabagenin (OGN), dihydro-ouabain (DHO), iso-ouabain (ISO), and a lactone ring opened analog (ORO) at 30 μg · kg-1 · 24 h-1 for 5 weeks via subcutaneous osmotic pumps. Cuff pressures were taken weekly. At the end of the study, trunk blood was harvested, extracted by C18 column, and subjected to high-performance liquid chromatography. Fractions were analyzed for OUA, OGN, and DHO by immunoassay. In OUA-, OGN-, and DHO-infused rats, 1 main peak of immunoreactivity corresponding to the infused agent was found. No evidence of in vivo conversion to OUA or DHO was found for any analog except ORO. At 5 weeks, systolic blood pressures in VEH, RHA, OUA, OGN, DHO, ISO, and ORO were 132±2.5, 133±1.5. 159±2.6,* 154±4,* 167±4,*† 171±2.2*† and 169±2.4*† mm Hg, respectively (*P

Original languageEnglish
Pages (from-to)472-477
Number of pages6
Issue number2 II
Publication statusPublished - 2001


  • Analogs and derivatives
  • Blood pressure
  • Glycosides
  • Sodium pump

ASJC Scopus subject areas

  • Internal Medicine


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