Brain natriuretic peptide: possible role in the modulation of hypoxic pulmonary hypertension.
To test the hypothesis that brain natriuretic peptide (BNP) plays a role similar to that of atrial natriuretic peptide (ANP) in modulating pulmonary vascular responses to hypoxia, we measured the vasodilator potency of ANP and BNP in rat pulmonary artery (PA) and thoracic aorta (TA) rings and in isolated rat lungs. We also measured the effect of chronic hypoxia on plasma levels and cardiac gene expression of both peptides. BNP had a vasorelaxant effect equipotent to that of ANP on preconstricted TA and PA rings, but was less potent than ANP in relaxing the vasoconstrictor response to hypoxia in isolated lungs [mean 50% inhibitory concentration (IC50) 10(-7) vs. 10(-6) M for ANP and BNP, respectively]. Plasma BNP levels were 30-fold lower than ANP, but both peptides increased approximately 70% during chronic hypoxia. In the right atrium, hypoxia lowered BNP mRNA slightly, but had no effect on ANP mRNA or tissue levels of either peptide. However, hypoxia increased right ventricular content and mRNA levels of both peptides by three- to fourfold. We conclude that BNP and ANP have similar pulmonary vasodilator effects and are upregulated proportionally during chronic hypoxia. These results support a role for BNP in modulating the pulmonary hypertensive response to chronic hypoxia.
Hill
N S
NS
Division of Pulmonary and Critical Care Medicine, Rhode Island Hospital, Providence.
Klinger
J R
JR
Warburton
R R
RR
Pietras
L
L
Wrenn
D S
DS
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001483:Base Sequence; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015345:Oligonucleotide Probes / Q000235:genetics; D011651:Pulmonary Artery / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D009419:Nerve Tissue Proteins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor