Zhang J S, Van Meel J C, Pfaffendorf M, Van Zwieten P A
Department of Pharmacotherapy, Academic Medical Centre, University of Amsterdam, The Netherlands.
Naunyn Schmiedebergs Arch Pharmacol. 1993 Feb;347(2):220-4. doi: 10.1007/BF00169271.
The purpose of the present study was to identify the angiotensin II-receptor subtype involved in the enhancement of the amplitude of the phasic contractions by angiotensin II in the isolated rat portal vein preparation. At an extracellular Ca2+ concentration of 0.9 mmol/l and a K+ concentration of 4 mmol/l, angiotensin II induced concentration-dependent increases in the amplitude of the phasic contractions. The enhancement of phasic contraction amplitude caused by angiotensin II was not significantly altered by pretreatment of the rat portal vein with indomethacin 10(-5) mol/l or nitro-L-arginine 10(-4) mol/l, indicating that neither prostaglandins nor the endothelium derived-relaxing factor (NO) are involved. Losartan (DuP 753), a nonpeptide selective AT1-receptor antagonist, concentration-dependently shifted the concentration-response curve for the effect of angiotensin II on the amplitude of the contractions to the right, without reducing the maximal response (pA2 = 8.6, slope = 0.98), thus suggesting competitive antagonism at the level of AT1-receptors. By contrast, PD 123,177, a nonpeptide selective AT2-receptor antagonist, even at 10(-5) mol/l, caused no significant change of the phasic myogenic response to angiotensin II, indicating the absence of AT2-receptor involvement. Dithiothreitol, a disulfide-reducing agent which is known to inactivate AT1-receptors in various tissues, markedly inhibited (3 mmol/l) or even abolished (5 mmol/l) the contractile response of the rat portal vein to angiotensin II, supporting the conclusion that these receptors can be classified as AT1-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究的目的是确定在离体大鼠门静脉标本中，血管紧张素II增强相性收缩幅度所涉及的血管紧张素II受体亚型。在细胞外Ca2+浓度为0.9 mmol/l和K+浓度为4 mmol/l时，血管紧张素II引起相性收缩幅度呈浓度依赖性增加。用10(-5) mol/l的吲哚美辛或10(-4) mol/l的硝基-L-精氨酸预处理大鼠门静脉，血管紧张素II引起的相性收缩幅度增强无明显改变，这表明前列腺素和内皮源性舒张因子（NO）均未参与。非肽选择性AT1受体拮抗剂氯沙坦（DuP 753）使血管紧张素II对收缩幅度影响的浓度-反应曲线浓度依赖性地右移，而不降低最大反应（pA2 = 8.6，斜率 = 0.98），因此提示在AT1受体水平存在竞争性拮抗作用。相比之下，非肽选择性AT2受体拮抗剂PD 123,177即使在10(-5) mol/l时，对血管紧张素II的相性肌源性反应也无明显改变，表明不存在AT2受体参与。二硫苏糖醇是一种已知能使各种组织中的AT1受体失活的二硫键还原剂，它能显著抑制（3 mmol/l）甚至消除（5 mmol/l）大鼠门静脉对血管紧张素II的收缩反应，支持这些受体可归类为AT1受体的结论。（摘要截短至250字）
