Abstract
BACKGROUND: The prevalence of cardiovascular diseases, especially heart failure, continues to rise worldwide. In heart failure, increasing levels of circulating atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are associated with a worsening of heart failure and a poor prognosis. AIM: To test whether a high concentration of BNP would inhibit relaxation to ANP. METHODS: Pulmonary arteries were dissected from disease-free areas of lung resection, as well as pulmonary artery rings of internal diameter 2.5-3.5 mm and 2 mm long, were prepared. Pulmonary artery rings were mounted in a multiwire myograph, and a basal tension of 1.61gf was applied. After equilibration for 60 min, rings were pre-constricted with 11.21 µmol/L PGF(2α) (EC(80)), and concentration response curves were constructed to vasodilators by cumulative addition to the myograph chambers. RESULTS: Although both ANP and BNP were found to vasodilate the pulmonary vessels, ANP is more potent than BNP. pEC50 of ANP and BNP were 8.96 ± 0.21 and 7.54 ± 0.18, respectively, and the maximum efficacy (E(max)) for ANP and BNP was -2.03 gf and -0.24 gf, respectively. After addition of BNP, the E(max) of ANP reduced from -0.96gf to -0.675gf (P = 0.28). CONCLUSION: BNP could be acting as a partial agonist in small human pulmonary arteries, and inhibits relaxation to ANP. Elevated levels of circulating BNP could be responsible for the worsening of decompensated heart failure. This finding could also explain the disappointing results seen in clinical trials of ANP and BNP analogues for the treatment of heart failure.