肾上腺素、去甲肾上腺素以及甲氧明对低氧性肺动脉高压模型大鼠肺动脉张力的影响

Effects of epinephrine, norepinephrine and methoxamine on pulmonary artery tension in a rat model of hypoxic pulmonary hypertension

目的评价肾上腺素(adrenaline,AD)、去甲肾上腺素(norepinephrine,NE)、甲氧明(methoxamine,MOX)对低氧性肺动脉高压模型大鼠肺动脉张力的影响。方法按照随机数字表法将48只雄性SD大鼠分为两组(每组24只):常氧对照组(C组)和低氧干预组(H组)。H组组放置于低氧箱(10%O2)中干预4周,C组放置于同一房间内,常压、常氧饲养4周,4周后分别测定两组大鼠体重、右心室收缩压(right ventricular systolic pressure,RVSP)、右颈总动脉压(mean circulating arterial pressure,mCAP),分离大鼠的肺动脉和肠系膜动脉,进行离体血管实验,比较AD、NE、MOX对两组大鼠肺动脉环和肠系膜动脉环的最大收缩张力和反应性。结果H组mCAP、体重低于C组,而RVSP高于C组(P<0.05)。H组AD、NE、MOX对肺动脉环的最大收缩张力均高于C组(P<0.05),C组和H组AD、NE、MOX对肠系膜动脉环的最大收缩张力较肺动脉环明显升高(P<0.05)。H组肺动脉环中AD、NE、MOX的ρEC50[半数有效浓度(median effective concentration,EC50)的负对数]值明显高于C组(P<0.05),MOX的ρEC50值较AD及NE的ρEC50值均偏低,差异有统计学意义(P<0.05)。结论正常大鼠肺动脉环和肠系膜动脉环对AD、NE、MOX均产生收缩反应,但肺动脉环较肠系膜动脉环收缩功能弱。在低氧性肺动脉高压模型中,肺动脉对AD、NE、MOX产生收缩反应,且较正常肺动脉环反应性和最大收缩张力更强。AD、NE对肺动脉环的反应性和最大收缩张力相似,而MOX与AD、NE相比,对肺动脉的收缩作用较弱。

Objective To evaluate the effects of adrenaline(AD),norepinephrine(NE)and methoxamine(MOX)on pulmonary artery tension in a rat model of hypoxic pulmonary hypertension.Methods According to the random number table method,48 male SD rats were divided into two groups(n=24):normoxia control group(group C)and hypoxia intervention group(group H).Rats in group H was placed in a hypoxic box(10%O2)for four weeks for intervention,rats in group C was placed in the same room and fed under normal pressure and normal oxygen for 4 weeks.After 4 weeks,the weight and right ventricular systolic pressure of the two groups of rats were measured.Right ventricular systolic pressure(RVSP),right common carotid artery pressure mean circulating arterial pressure(mCAP),isolate the rat's pulmonary artery and mesenteric artery,conduct an isolated blood vessel experiment,compared AD,NE,MOX on pulmonary artery of two groups of rats.The maximum contractile tension and contractile responsiveness of the ring and the mesenteric artery ring.Results Compared with group C,group H presented remarkably decreased right common carotid arterial pressure and body weight(P<0.05)and increased RVSP(P<0.05).Group H presented higher maximum contraction efficacy of the pulmonary artery ring towards AD,NE and MOX than group C(P<0.05).In group C and group H,the maximum contraction efficacy of AD,NE,and MOX towards the mesenteric artery ring was remarkably higher than those towards the pulmonary artery ring(P<0.05).Compared with group C,theρEC50[negative logarithm of the median effective concentration(EC50)molar concentration]value of AD,NE,and MOX in the pulmonary artery ring markedly increased in group H(P<0.05),theρEC50 value of MOX were lower than those of AD and NE,with statistical difference(P<0.05).Conclusions In normal rats,the pulmonary artery ring and mesenteric artery ring have contractile responses towards AD,NE and MOX,with relative weak contraction function in the pulmonary artery ring.In the hypoxic pulmonary hypertension model,the pulmonary artery produces a contractile response to AD,NE,and MOX,which is stronger than normal pulmonary artery ring reactivity and maximum contraction efficacy.AD and NE have similar responsiveness and the maximum contraction tension towards the pulmonary artery ring.Compared with AD and NE,MOX has a weaker contraction effect on the pulmonary artery.