Advertisement
Research Article| Volume 76, ISSUE 2, P280-292, August 1970

Download started.

Ok

Renal mechanisms of the natriuretic and antiphosphaturic effects of triflocin—a new diuretic

  • Zalman S. Agus
    Footnotes
    Affiliations
    From the Renal Section, Department of Medicine, University of Pennsylvania, School of Medicine Philadelphia, Pa., USA
    Search for articles by this author
  • Martin Goldberg
    Correspondence
    Reprint requests: Martin Goldberg, M.D., 860 Gates Building, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, Pa. 19104.
    Affiliations
    From the Renal Section, Department of Medicine, University of Pennsylvania, School of Medicine Philadelphia, Pa., USA
    Search for articles by this author
  • Author Footnotes
    ∗ Dr. Agus was a Postdoctoral Fellow supported by United States Public Health Grant No. 1 F3AM-38,709 from July 1968 to June 1969.
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Acute clearance studies were performed in normal volunteers to determine the renal sites and mechanism of action of triflocin, a structurally new diuretic. The drug was found to be a moderately to markedly potent natriuretic agent, producing a maximal fractional sodium excretion which varied between 0.04 and 0.12. The natriuresis was associated with both an inhibition in free water clearance (CH2O) during sustained water diuresis and a reduction in solute-free water reabsorption (TcH2O) when superimposed upon a hypertonic saline diuresis during hydropenia, indicating a major site of action in the ascending limb of the loop of Henle. In addition, triflocin was found to produce a fall in glomerular filtration rate (10 to 15 per cent), unrelated to volume depletion, and a consistent but variable decrease in fractional phosphate excretion. The enhanced tubular phosphate reabsorption, an effect not previously described with other diuretics, is felt to be mediated by enhanced reabsorption of sodium in the proximal tubule, either by direct tubular action or via hemodynamic changes.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Translational Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Cummings J.B.
        • Ronsberg M.A.
        • Stokey E.H.
        • Gussin R.Z.
        Pharmocodynamics of 4-(α,α,α-trifluoro-m-(toluidino)-nicotinic acid), a diuretic with high ceiling activity.
        Pharmacologist. 1968; 10: 162
        • Gussin R.A.
        • Cummings J.R.
        • Stokey E.H.
        • Ronsberg M.A.
        Cl 65,562 (4-(α,α,α-trifluoro-m-toluidino)-nicotinic acid). A novel “high ceiling” diuretic.
        J. Pharm. Exp. Ther. 1969; 167: 194
        • Goldberg M.
        • McCurdy D.K.
        • Foltz E.L.
        • Bluemle Jr., L.W.
        Effect of ethacrynic acid (a new saluretic agent) on renal diluting and concentrating mechanisms: Evidence for site of action in the loop of Henle.
        J. Clin. Invest. 1964; 43: 201
        • Puschett J.B.
        • Goldberg M.
        The acute effects of furosemide on acid and electrolyte excretion in man.
        J. Lab. Clin. Med. 1968; 71: 666
        • Goldberg M.
        • McCurdy D.K.
        • Ramirez M.A.
        Differences between saline and mannitol diuresis in hydropenic man.
        J. Clin. Invest. 1965; 44: 182
        • Berliner R.W.
        • Bennett C.M.
        Concentration of urine in the mammalian kidney.
        Amer. J. Med. 1967; 42: 777
        • Earley L.E.
        • Kahn M.
        • Orloff J.
        The effects of infusions of chlorothiazide on urinary dilution and concentration in the dog.
        J. Clin. Invest. 1961; 40: 857
        • Suki W.
        • Rector Jr., F.C.
        • Seldin D.W.
        The site of action of furosemide and other sulfonamide diuretics in the dog.
        J. Clin. Invest. 1965; 44: 1458
        • Johnston G.S.
        • Murphy G.P.
        The effects of ethacrynic acid diuresis on renal hemodynamics and Hg203 chlormerodrin excretion.
        J. Surg. Res. 1967; 7: 215
        • Ludens J.H.
        • Hook J.B.
        • Brody M.J.
        • Williamson H.E.
        Enhancement of renal blood flow by furosemide.
        J. Pharm. Exp. Ther. 1968; 163: 456
        • Strickler J.C.
        • Thompson D.D.
        • Klose R.M.
        • Giebisch G.
        Micropuncture study of inorganic phosphate excretion in the rat.
        J. Clin. Invest. 1964; 43: 1596
        • Massry S.G.
        • Coburn J.W.
        • Kleeman C.R.
        The influence of extracellular volume expansion on renal phosphate reabsorption in the dog.
        J. Clin. Invest. 1969; 48: 1237
        • Suki W.N.
        • Martinez-Maldonado M.
        • Rowe D.
        • Terry A.
        Effect of expansion of extracellular fluid volume on renal phosphate handling.
        J. Clin. Invest. 1969; 48: 1888
        • Puschett J.B.
        • Agus Z.S.
        • Senesky D.J.
        • Goldberg M.
        Mechanism of action of parathyroid hormone in dog proximal tubule.
        J. Clin. Invest. 1970; (Abst.) In press
        • Dirks J.H.
        • Cirksena W.J.
        • Berliner R.W.
        Micropuncture study of the effect of various diuretics on sodium reabsorption by the proximal tubules of the dog.
        J. Clin. Invest. 1966; 45: 1875
        • Brenner B.M.
        • Keimowitz R.I.
        • Wright F.S.
        • Berliner R.W.
        An inhibitory effect of furosemide on sodium reabsorption by the proximal tubule of the rat nephron.
        J. Clin. Invest. 1969; 48: 290
        • Levine D.Z.
        • Liebau G.
        • Fischbach H.
        • Thurau K.
        Micropuncture studies on the dog kidney. II. Reabsorptive characteristics of the proximal tubule during spontaneous and experimental variations in GFR and during drug induced natriuresis.
        Pflueger. Arch. 1968; 304: 365
        • Pitts R.F.
        • Alexander R.S.
        The renal absorptive mechanism for inorganic phosphate in normal and acidotic dogs.
        Amer. J. Physiol. 1944; 142: 648
        • Slatopolosky E.
        • Gradowska L.
        • Kashemsant C.
        • Keltner R.
        • Manley C.
        • Bricker N.S.
        The control of phosphate excretion in uremia.
        J. Clin. Invest. 1966; 45: 672
        • Brenner B.M.
        • Bennett C.M.
        • Berliner R.W.
        The relationship between glomerular filtration rate and sodium reabsorption by the proximal tubule of the rat nephron.
        J. Clin. Invest. 1968; 47: 1358
        • Knox F.G.
        • Wright F.S.
        • Howards S.S.
        • Berliner R.W.
        Effect of furosemide on sodium reabsorption by proximal tubule of the dog.
        Amer. J. Physiol. 1969; 217: 192
        • Earley L.E.
        • Dougharty T.W.
        Sodium metabolism.
        New Eng. J. Med. 1969; 281: 72
        • Krishna G.
        • Weiss B.
        • Davies R.L.
        • Hynie S.
        Mechanism of nicotinic acid inhibition of hormone-induced lipolysis.
        in: Fed. Proc. 25. 1966: 719 (Abst.)
        • Rasmussen H.
        • Pechet M.
        • Fast D.
        Effect of dibutyryl cyclic adenosine 3′5′-monophosphate, theophylline, and other nucleotides upon calcium and phosphate metabolism.
        J. Clin. Invest. 1968; 47: 1843