Renal hyporesponsiveness to brain natriuretic peptide: both generation and renal activity of cGMP are decreased in patients with pulmonary hypertension.
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.
Charloux
Anne
A
Institut de Physiologie, Service de Physiologie et d'Explorations Fonctionnelles et EA 3072, 4 rue Kirschleger, 67085 Strasbourg Cedex, France. Anne.Charloux@chru-strasbourg.fr
Chaouat
Ari
A
Piquard
François
F
Brandenberger
Gabrielle
G
Weitzenblum
Emmanuel
E
Geny
Bernard
B
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000378:metabolism; D006152:Cyclic GMP / Q000097:blood / Q000378:metabolism* / Q000652:urine; D015536:Down-Regulation; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000494:pharmacology*; D012016:Reference Values; D051437:Renal Insufficiency / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*; D012083:Renin / Q000097:blood; D015398:Signal Transduction; D012965:Sodium Chloride
D020097:Natriuretic Peptide, Brain; D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor; D003404:Creatinine; D012083:Renin; D006152:Cyclic GMP