Differential effects of atrial and brain natriuretic peptides on human pulmonary artery:An in vitro study

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 11.21μmol/L PGF2α(EC80),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(Emax)for ANP and BNP was-2.03 gf and-0.24 gf,respectively.After addition of BNP,the Emax 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.

Characterization of optimal resting tension in human pulmonary arteries

AIM To determine the optimum resting tension(ORT) for in vitro human pulmonary artery(PA) ring preparations.METHODS Pulmonary arteries were dissected from disease free sections of the resected lung in the operating theatre and tissue samples were directly sent to the laboratory in Krebs-Henseleit solution(Krebs).The pulmonary arteries were then cut into 2 mm long rings.PA rings were mounted in 25 m L organ baths or 8 m L myograph chambers containing Krebs compound(37 ℃,bubbled with 21% O_2:5% CO_2) to measure changes in isometric tension.The resting tension was set at 1-gram force(gf) with vessels being left static to equilibrate for duration of one hour.Baseline contractile reactions to 40 mmol/L KCl were obtained from a resting tension of 1 gf.Contractile reactions to 40 mmol/L KCl were then obtained from stepwise increases in resting tension(1.2,1.4,1.6,1.8 and 2.0 gf).RESULTS Twenty PA rings of internal diameter between 2-4 mmwere prepared from 4 patients.In human PA rings incrementing the tension during rest stance by 0.6 gf,up to 1.6 gf significantly augmented the 40 mmol/L KCl stimulated tension.Further enhancement of active tension by 0.4 gf,up to 2.0 gf mitigate the 40 mmol/L KCl stimulated reaction.Both Myograph and the organ bath demonstrated identical conclusions,supporting that the radial optimal resting tension for human PA ring was 1.61 g.CONCLUSION The radial optimal resting tension in our experiment is 1.61 gf(15.78 m N) for human PA rings.