title: Reversal of atrial natriuretic peptide resistance by increasing distal tubular sodium delivery in patients with decompensated cirrhosis.
abstract: To test the hypothesis that diminished sodium delivery to the distal tubular site of atrial natriuretic peptide (ANP) action accounts for renal ANP resistance in cirrhosis, 12 cirrhotic patients with ascites were studied at baseline and during the infusion of ANP alone (0.15 micrograms/kg/min), mannitol alone (4 g/hr), and ANP plus mannitol for 3 hours each. Distal tubular sodium delivery, as assessed by lithium clearance, was increased during the infusion of mannitol (13.8 +/- 3.4 to 23.7 +/- 5.7 mL/min; P < .05) and during the ANP plus mannitol infusion (13.8 +/- 3.4 to 28.5 +/- 6.3 mL/min; P < .001) in 6 patients, subsequently termed "responders." Both responders and nonresponders were resistant to the natriuretic effect of ANP infused alone, and mannitol alone did not produce an increase in urinary sodium excretion. However, in responders, the mannitol-induced increase in distal tubular sodium delivery resulted in a fivefold increase in urinary sodium excretion during ANP infusion (29 +/- 6 to 154 +/- 40 mumol/min, P < .01). Urinary cyclic guanosine monophosphate (cGMP) excretion increased significantly and to a similar extent during ANP and ANP plus mannitol in all 12 patients, supporting the active biological responsiveness of renal ANP receptors. Unlike responders, nonresponders showed a significant decrease in arterial blood pressure and an increase in plasma renin activity during ANP plus mannitol, consistent with worsened arterial underfilling caused by ANP-induced vasodilation. Thus, the present results support the hypothesis that diminished distal tubular sodium delivery is a major factor contributing to ANP resistance in cirrhosis.
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Denver 80262, USA.
authors.forename: W T
authors.initials: WT
authors.lastname: Abraham
authors.forename: M E
authors.initials: ME
authors.lastname: Lauwaars
authors.forename: J K
authors.initials: JK
authors.lastname: Kim
authors.forename: R L
authors.initials: RL
authors.lastname: Peña
authors.forename: R W
authors.initials: RW
authors.lastname: Schrier
mesh_terms: D000328:Adult; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use*; D001682:Biological Availability; D006152:Cyclic GMP / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007686:Kidney Tubules, Distal / Q000503:physiopathology*; D008094:Lithium / Q000097:blood; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008353:Mannitol / Q000627:therapeutic use; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D014556:Urine / Q000502:physiology
chemical_list: D008353:Mannitol; D009320:Atrial Natriuretic Factor; D008094:Lithium; D012964:Sodium; D006152:Cyclic GMP