Hussain Azar, Bennett Robert T, Tahir Zaheer, Isaac Emmanuel, Chaudhry Mubarak A, Qadri Syed S, Loubani Mahmoud, Morice Alyn H
Department of Cardiothoracic Surgery, Castle Hill Hospital, Cottingham HU16 5JQ, United Kingdom.
Centre for Cardiovascular and Metabolic Research, Hull York Medical School, Castle Hill Hospital, Cottingham HU16 5JQ, United Kingdom.
World J Cardiol. 2019 Oct 26;11(10):236-243. doi: 10.4330/wjc.v11.i10.236.
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.
To test whether a high concentration of BNP would inhibit relaxation to ANP.
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 (EC), and concentration response curves were constructed to vasodilators by cumulative addition to the myograph chambers.
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) for ANP and BNP was -2.03 gf and -0.24 gf, respectively. After addition of BNP, the E of ANP reduced from -0.96gf to -0.675gf ( = 0.28).
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.
心血管疾病，尤其是心力衰竭的患病率在全球范围内持续上升。在心力衰竭中，循环中的心房利钠肽（ANP）和脑利钠肽（BNP）水平升高与心力衰竭的恶化及不良预后相关。
测试高浓度的BNP是否会抑制对ANP的舒张反应。
从肺切除的无病区域解剖肺动脉，并制备内径为2.5 - 3.5毫米、长2毫米的肺动脉环。将肺动脉环安装在多线肌张力描记仪中，并施加1.61gf的基础张力。平衡60分钟后，用11.21μmol/L的前列腺素F（EC）预收缩，通过向肌张力描记仪腔室中累积添加血管舒张剂构建浓度反应曲线。
尽管发现ANP和BNP均可使肺血管舒张，但ANP比BNP更有效。ANP和BNP的pEC50分别为8.96±0.21和7.54±0.18，ANP和BNP的最大效应（E）分别为 - 2.03gf和 - 0.24gf。添加BNP后，ANP的E从 - 0.96gf降至 - 0.675gf（P = 0.28）。
BNP可能在人小肺动脉中作为部分激动剂起作用，并抑制对ANP的舒张反应。循环中BNP水平升高可能是失代偿性心力衰竭恶化的原因。这一发现也可以解释在ANP和BNP类似物治疗心力衰竭的临床试验中所看到的令人失望的结果。
