Renal hyporesponsiveness to brain natriuretic peptide: both generation and renal activity of cGMP are decreased in patients with pulmonary hypertension

Peptides. 2006 Nov;27(11):2993-9. doi: 10.1016/j.peptides.2006.05.023. Epub 2006 Jul 5.

Abstract

We examined the mechanisms of renal resistance to atrial and brain natriuretic peptides (ANP and BNP) in pulmonary hypertension (PH). Compared to eight controls, nine PH patients showed a reduced ability to excrete an acute sodium load despite increased circulating ANP, BNP and cyclic guanosine monophosphate (cGMP), their second messenger. Patients' reduced urinary cGMP/BNP and natriuresis/urinary cGMP ratios demonstrated impaired generation of and reduced renal response to cGMP, respectively. Therefore, PH patients hyporesponsiveness to cardiac natriuretic peptides is likely located both upstream and downstream cGMP generation. Natriuretic peptide signalling pathway disruptions might be accessible to therapy.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atrial Natriuretic Factor / blood
  • Atrial Natriuretic Factor / urine
  • Creatinine / metabolism
  • Cyclic GMP / blood
  • Cyclic GMP / metabolism*
  • Cyclic GMP / urine
  • Down-Regulation
  • Female
  • Humans
  • Hypertension, Pulmonary / complications
  • Hypertension, Pulmonary / physiopathology*
  • Kidney / drug effects*
  • Kidney / metabolism*
  • Male
  • Middle Aged
  • Natriuresis / drug effects
  • Natriuretic Peptide, Brain / blood
  • Natriuretic Peptide, Brain / pharmacology*
  • Reference Values
  • Renal Insufficiency / complications
  • Renal Insufficiency / diagnosis
  • Renal Insufficiency / physiopathology*
  • Renin / blood
  • Signal Transduction
  • Sodium Chloride

Substances

  • Natriuretic Peptide, Brain
  • Sodium Chloride
  • Atrial Natriuretic Factor
  • Creatinine
  • Renin
  • Cyclic GMP