BRAIN NATRIURETIC PEPTIDE - POSSIBLE ROLE IN THE MODULATION OF HYPOXIC PULMONARY-HYPERTENSION

To test the hypothesis that brain natriuretic peptide (BNP) plays a ro le similar to that of atrial natriuretic peptide (ANP) in modulating p ulmonary vascular responses to hypoxia, we measured the vasodilator po tency 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 ch ronic hypoxia on plasma levels and cardiac gene expression of both pep tides. BNP had a vasorelaxant effect equipotent to that of ANP on prec onstricted TA and PA rings, but was less potent than ANP in relaxing t he vasoconstrictor response to hypoxia in isolated lungs [mean 50% inh ibitory concentration (IC50) 10(-7) vs. 10(-6) M for ANP and BNP, resp ectively]. Plasma BNP levels were 30-fold lower than ANP, but both pep tides increased similar to 70% during chronic hypoxia. In the right at rium, 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 four fold. We conclude that BNP and ANP have similar pulmonary vasodilator effects and are upregulated proportionally during chronic hypoxia. The se results support a role for BNP in modulating the pulmonary hyperten sive response to chronic hypoxia.