title: Pressure-dependent distal tubular action of atrial natriuretic peptide in healthy humans.
abstract: OBJECTIVE
  To study the influence of blood pressure reduction with sodium nitroprusside on the renal glomerular and tubular actions of atrial natriuretic peptide.
  
  
  METHODS
  Forty-nine healthy subjects were examined in four different groups receiving placebo, sodium nitroprusside alone, atrial natriuretic peptide alone (10 ng/kg per min), or sodium nitroprusside and atrial natriuretic peptide in combination. The infusion rate of sodium nitroprusside was gradually increased until a 10 mmHg decrease in diastolic blood pressure was obtained.
  
  
  METHODS
  Lithium clearance was used to evaluate segmental tubular reabsorption.
  
  
  RESULTS
  In the placebo group neither renal nor hormonal parameters were changed. Except for a fall in urinary flow, sodium nitroprusside alone had no effect on renal parameters. Urinary excretion of cyclic GMP (cGMP) was slightly increased, whereas the plasma cGMP level was not changed in response to sodium nitroprusside. The plasma aldosterone level was elevated during sodium nitroprusside infusion, although neither the plasma angiotensin II level nor the plasma atrial natriuretic peptide level were changed. Atrial natriuretic peptide alone caused an increase in filtration fraction and a decrease in renal plasma flow. Urinary sodium excretion, fractional sodium excretion, and urinary flow were increased, and distal fractional tubular sodium absorption decreased, whereas lithium clearance and proximal fractional tubular re-absorption were not changed by atrial natriuretic peptide. Atrial natriuretic peptide alone caused a decrease in plasma aldosterone and an increase in plasma and urinary cGMP levels. During blood pressure reduction with sodium nitroprusside, atrial natriuretic peptide caused no changes in the renal parameters except for an increase in filtration fraction. Thus, the increase in urinary sodium excretion (-8 versus +37 micromol/min) and the decrease in distal fractional sodium excretion (0.0 versus -2.4%) caused by atrial natriuretic peptide were attenuated. The atrial natriuretic peptide-induced changes in proximal fractional tubular reabsorption (-0.5 versus +0.6%) and cGMP were not changed by blood pressure reduction.
  
  
  CONCLUSIONS
  Blood pressure reduction causes an attenuation of the natriuretic action of atrial natriuretic peptide in normotensive humans that is at least partly caused by attenuation of the distal tubular action of atrial natriuretic peptide. The results support the hypothesis that the action of atrial natriuretic peptide on distal tubular sodium reabsorption is pressure-dependent in humans.
authors.affiliation: Department of Medicine and Nephrology C, Skejby Hospital, Arhus, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Eiskjaer
authors.forename: C B
authors.initials: CB
authors.lastname: Nielsen
authors.forename: E B
authors.initials: EB
authors.lastname: Pedersen
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007684:Kidney Tubules / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D009599:Nitroprusside; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP