Zhou Yingbi, Dirksen Wessel P, Babu Gopal J, Periasamy Muthu
Department of Physiology and Cell Biology, Ohio State Univ. College of Medicine and Public Health, Columbus, OH 43210, USA.
Am J Physiol Heart Circ Physiol. 2003 Dec;285(6):H2797-803. doi: 10.1152/ajpheart.00466.2003. Epub 2003 Aug 7.
Genetically altered mice are increasingly used as experimental models. However, ANG II responses in mouse blood vessels have not been well defined. Therefore, the aim of this study was to determine the role of ANG II in regulating major blood vessels in C57/BL6J mice with isometric force measurements. Our results showed that in mouse abdominal aorta ANG II induced a concentration-dependent contraction (EC50 4.6 nM) with a maximum contraction of 75.1 +/- 4.9% at 100 nM compared with that of 60 mM K+. Similarly, femoral artery also exhibited a contractile response of 76.0 +/- 3.4% to the maximum concentration of ANG II (100 nM). In contrast, ANG II (100 nM)-induced contraction was significantly less in carotid artery (24.5 +/- 6.6%) and only minimal (3.5 +/- 0.31%) in thoracic aorta. The nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester and the AT2 antagonist PD-123319 failed to enhance ANG II-induced contractions. However, an AT1 antagonist, losartan (10 microM), completely inhibited ANG II (100 nM) response in abdominal aorta and carotid artery. An AT1 agonist, [Sar1]-ANG II (100 nM), behaved similarly to ANG II (100 nM) in abdominal aorta and carotid artery. RT-PCR analyses showed that mouse thoracic aorta has a significantly lower AT1 mRNA level than abdominal aorta. These results demonstrate that major mouse vessels exhibit differential contractions to ANG II, possibly because of varied AT1 receptor levels.
基因改造小鼠越来越多地被用作实验模型。然而，小鼠血管中血管紧张素II（ANG II）的反应尚未得到很好的界定。因此，本研究的目的是通过等长力测量来确定ANG II在调节C57/BL6J小鼠主要血管中的作用。我们的结果表明，在小鼠腹主动脉中，ANG II诱导浓度依赖性收缩（半数有效浓度[EC50]为4.6 nM），与60 mM K+相比，在100 nM时最大收缩率为75.1±4.9%。同样，股动脉对ANG II的最大浓度（100 nM）也表现出76.0±3.4%的收缩反应。相比之下，ANG II（100 nM）诱导的颈动脉收缩明显较小（24.5±6.6%），胸主动脉中仅为最小收缩（3.5±0.31%）。一氧化氮合酶抑制剂Nω-硝基-L-精氨酸甲酯和AT2拮抗剂PD-123319未能增强ANG II诱导的收缩。然而，AT1拮抗剂氯沙坦（10 μM）完全抑制了腹主动脉和颈动脉中ANG II（100 nM）的反应。AT1激动剂[Sar1]-ANG II（100 nM）在腹主动脉和颈动脉中的表现与ANG II（100 nM）相似。逆转录聚合酶链反应（RT-PCR）分析表明，小鼠胸主动脉的AT1 mRNA水平明显低于腹主动脉。这些结果表明，小鼠主要血管对ANG II表现出不同的收缩反应，可能是由于AT1受体水平不同。
