Impaired release of bioactive parathyroid hormone-related peptide in patients with pulmonary hypertension and endothelial dysfunction.
BACKGROUND
Parathyroid hormone-related protein (PTHrP) is an endothelial-derived vasoactive peptide. This study investigated whether bioactive PTHrP is locally released in a pressure-dependent way.


METHODS
A PTHrP antibody directed against the midregional part of PTHrP was used to analyze PTHrP in plasma samples. The biological activity of this PTHrP-like peptide was investigated in vitro. Plasma values were determined in samples from the left pulmonary artery and the arteria femoralis, taken under basal conditions and after the application of oxygen or iloprost to lower the pulmonary pressure. Twenty young patients (mean age 6.5 years), who were catheterized for an analysis of the reactivity of the pulmonary bed, were investigated. Endothelial function was investigated by acetylcholine responsiveness.


RESULTS
The antibody recognized a 30-kDa protein with in vitro PTHrP-like activity. In 11 patients (responders) with intact endothelial function, the PTHrP values determined in the left pulmonary artery were higher than those in the arteria femoralis. The local increase in the PTHrP concentration was reduced when either oxygen or iloprost lowered the pressure. Nine patients with endothelial dysfunction did not show any concentration gradients at any time (nonresponders).


CONCLUSIONS
The local concentration of bioactive PTHrP is increased in patients with pulmonary hypertension and normal endothelial function.
Sokolova
Juliana
J
Institut für Physiologie, Justus Liebig University Giessen, Aulweg 129, DE-35392 Giessen, Germany.
Zimmermann
Rainer
R
Kreuder
Joachim
J
Michel-Behnke
Ina
I
Schranz
Dietmar
D
Piper
Hans Michael
HM
Schluter
Klaus-Dieter
KD
D000109:Acetylcholine / Q000494:pharmacology; D000293:Adolescent; D001794:Blood Pressure; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000503:physiopathology; D016285:Iloprost / Q000494:pharmacology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D040542:Mechanotransduction, Cellular; D010100:Oxygen / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein / Q000097:blood*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D014665:Vasodilator Agents / Q000494:pharmacology
D044162:Parathyroid Hormone-Related Protein; D014665:Vasodilator Agents; D016285:Iloprost; D000109:Acetylcholine; D010100:Oxygen