尼索地平对大鼠离体肺动脉和肺动脉高压的影响

Effects of Nisoldipine on the Contractile Response of Rats’ Isolated Pulmonary Arteris and Pulmonary Hypertention

关键词:  尼索地平  硝苯地平  肺动脉高压  KCl  去氧肾上腺素  大鼠肺动脉

Key words:  nisoldipine  nifedipine  pulmonary hypertention  KCl  phenylephrine  rat pulmonary artery

摘要:

目的 观察尼索地平(nifedipine，NIS)对KCl和去氧肾上腺素(phenylephrine，PHE)所致离体大鼠肺动脉收缩的作用，同时研究其对野百合碱诱导的肺动脉高压(pulmonary hypertention，PH)大鼠的影响。方法 ①采用离体血管实验法，以KCl和PHE在含钙离子和不含钙离子的K-H液中预收缩离体大鼠肺动脉环，观察NIS对血管收缩的影响。②取40只Wistar大鼠随机分为正常组、模型组、NIS组和硝苯地平(NIF)组，每组10只，采用野百合碱(50 mg·kg^-1)皮下注射建立大鼠PH模型，连续灌胃给药21 d。采用右心导管法测定mPAP、mRVP、maxPAP和maxRVP，并计算各组大鼠的RVHI和LI。结果 ①在含钙离子的K-H液中，NIS抑制KCl(20，40，60 mmol·L^-1)和PHE(1×10^-7，5×10^-7，1×10^-6 mol·L^-1)所致血管收缩的IC₅₀分别为0.87×10^-8，1.41×10^-8，8.32×10^-8 mol·L^-1和0.56×10^-7，4.27×10^-7，1.28×10^-6 mol·L^-1。在无钙离子K-H液中，NIS无抑制离体血管收缩的作用。②模型组大鼠mPAP、mRVP、maxPAP、maxRVP、RVHI和LI均显著高于正常组(P<0.01)，NIS组和NIF组大鼠的上述指标均显著低于模型组(P<0.05)。结论 NIS有抑制大鼠肺动脉收缩的作用，对野百合碱诱导的大鼠PH有治疗作用。

Abstract:

OBJECTIVE To observe the effects of nisoldipine(NIS) on the contractile response of isolated rat pulmonary artery induced by KCl and phenylephrine(PHE) and explore the effect of nisoldipine on monocrotaline-induced pulmonary hypertention(PH) in rats. METHODS ①Isolated artery experiment was used to observe the antagonistic effects of NIS on the contraction of isolated rats’ pulmonary arteris induced by KCl and PHE in the calciferous and calcium-free K-H solution. ②Forty Wistar rats were randomly divided into 4 groups: normal group, modle group , NIS group and nifedipine(NIF) group. Rats except those in normal group were injected with a single dose of moncrotaline(50 mg·kg^-1) to induce PH. Rats in each group were administrated with corresponding drugs for 21 d. The mPAP, mRVP, maxPAP and maxRVP were measured by right cardiac catheterization, and RVHI and LI were calculated. RESULTS ①In the calciferous K-H solution, the contractile response of rats’ isolated pulmonary arteris induced by KCl(20, 40, 60 mmol·L^-1) and PHE(1×10^-7, 5×10^-7, 1×10^-6 mol·L^-1) were inhibited by NIS. The IC₅₀ was 0.87×10^-8, 1.41×10^-8, 8.32×10^-8 mol·L^-1 and 0.56×10^-7，4.27×10^-7，1.28×10^-6 mol·L^-1, respectively. In the calcium-free K-H solution, NIS had no effect. ②The mPVP, mRVP, maxPAP, maxRVP, RVHI and LI in model group were higher than those of the normal group(P<0.01), and the above indexes in NIS group and NIF group were lower than those of the model group(P<0.05). CONCLUSION NIS can inhibit the contractile response of rats’ isolated pulmonary artery, and it has therapeutical effect on monocrotaine-induced pulmonary hypertension in rats.