Zhao L, Hughes J M, Winter R J
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Am Rev Respir Dis. 1992 Nov;146(5 Pt 1):1198-201. doi: 10.1164/ajrccm/146.5_Pt_1.1198.
We have studied the acute effect of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) on pulmonary vascular tone in normoxia and acute hypoxia in the absence and presence of a specific inhibitor of neutral endopeptidase 24.11 (NEI, UK 73, 967, candoxatrilat; Pfizer) in the isolated and blood-perfused rat lung preparation. Baseline pulmonary artery pressure (Ppa) was 16.4 +/- 0.3 mm Hg in lungs from normoxic control rats and 22.5 +/- 0.3 mm Hg in lungs from rats kept in hypoxia (FIO2 = 10%) for 7 days. Acute hypoxic pulmonary vasoconstriction (HPV delta Ppa) was similar in normoxic control rats (9.5 +/- 0.6 mm Hg) and chronically hypoxic rats (9.8 +/- 0.9 mm Hg). NEI at 0.07 and 0.2 mg had no effect on baseline Ppa or HPV delta Ppa. Synthetic BNP at 10 nM had no effect on baseline Ppa but produced a 2.8 +/- 0.2 mm Hg reduction in HPV delta Ppa alone and 2.7 +/- 0.2 mm Hg reduction in the presence of 0.07 mg NEI in normoxic control rats. In contrast, ANP at 10 nM produced a significantly greater decrease in HPV delta Ppa in the presence of 0.07 mg NEI (4.8 +/- 0.3 mm Hg, p < 0.05) compared with ANP alone (2.9 +/- 0.4 mm Hg), and similar results were also observed in chronically hypoxic rats. Thus, BNP has a vasodilator effect similar to that of ANP in the pulmonary circulation. Inhibition of neutral endopeptidase 24.11 augments the effects of ANP on HPV but does not influence the pulmonary vascular responses to BNP.
我们研究了在常氧和急性缺氧条件下，脑钠肽（BNP）和心房钠尿肽（ANP）对肺血管张力的急性影响，实验采用分离并灌注血液的大鼠肺标本，且分别在存在和不存在中性内肽酶24.11（NEI，UK 73,967，坎多沙坦酯；辉瑞公司）特异性抑制剂的情况下进行。常氧对照大鼠肺的基线肺动脉压（Ppa）为16.4±0.3 mmHg，在低氧（FIO2 = 10%）环境中饲养7天的大鼠肺的基线肺动脉压为22.5±0.3 mmHg。常氧对照大鼠（9.5±0.6 mmHg）和慢性低氧大鼠（9.8±0.9 mmHg）的急性低氧性肺血管收缩（HPV ΔPpa）相似。0.07 mg和0.2 mg的NEI对基线Ppa或HPV ΔPpa均无影响。10 nM的合成BNP对基线Ppa无影响，但单独使用时可使常氧对照大鼠的HPV ΔPpa降低2.8±0.2 mmHg，在存在0.07 mg NEI的情况下可降低2.7±0.2 mmHg。相比之下，10 nM的ANP在存在0.07 mg NEI时使HPV ΔPpa的降低幅度（4.8±0.3 mmHg，p < 0.05）明显大于单独使用ANP时（2.9±0.4 mmHg），在慢性低氧大鼠中也观察到了类似结果。因此，BNP在肺循环中具有与ANP相似的血管舒张作用。抑制中性内肽酶24.11可增强ANP对HPV的作用，但不影响肺血管对BNP的反应。
