Peral de Bruno M, Coviello A
Departamento de Fisiologia, Facultad de Medicina, Universidad Nacional de Tucumán, Argentina.
J Comp Physiol B. 1996;165(7):565-70. doi: 10.1007/BF00387518.
The effects of peptide and non-peptide angiotensin II receptor antagonists on the responses to angiotensin II were examined using aortic rings and skin isolated from the toad. The contractile responses of aortic rings to (Ala-Pro-Gly) angiotensin II were inhibited by angiotensin II analogue Leu8 angiotensin II, with a pA2 value of 7.6. Similarly, the concentration response curve for (Ala-Pro-Gly) angiotensin II was displaced to the right by the specific angiotensin receptor subtype antagonist DuP 753, with a pA2 value of 6.0. In contrast, the angiotensin receptor subtype 2 antagonists PD 123177 and CGP 42112A did not modify the contractile response to (Ala-Pro-Gly) angiotensin II. None of the antagonists was able to alter the contractile response to norepinephrine. Both Leu8 angiotensin II (10(-8) mol.1(-1)) and DuP 753 (10(-6) mol.1(-1)) partially inhibited angiotensin III-induced contractions in toad aorta. Angiotensin III, in turn, exhibited lower activity than [Asn1-Val5] angiotensin II in this preparation, its molar potency ratio being 0.293. Previous work from this laboratory reported that osmotic water permeability in the skin of the toad Bufo arenarum was increased by angiotensin II, the effect being blocked by the peptide antagonist Leu8 angiotensin II. The hydrosmotic response to [Asn1-Val5] angiotensin II(10(-7) mol.1(-1)) was significantly inhibited by DuP 753 (10(-6) and 5 x 10(-6) mol.1(-1)), whereas the response was not inhibited by a tenfold higher concentration of either PD 123177 or CGP 42112A. DuP 753 (10(-6) mol.1(-1) also inhibited the hydrosmotic response to angiotensin III (10(-7) mol.1(-1)). These results suggest that receptors for angiotensin II present isolated toad aorta and skin exhibit pharmacological features similar to those characterized as angiotensin subtype 1 in mammalian tissues.
使用从蟾蜍分离的主动脉环和皮肤，研究了肽类和非肽类血管紧张素II受体拮抗剂对血管紧张素II反应的影响。血管紧张素II类似物Leu8血管紧张素II抑制了主动脉环对（丙氨酸-脯氨酸-甘氨酸）血管紧张素II的收缩反应，其pA2值为7.6。同样，特异性血管紧张素受体亚型拮抗剂DuP 753使（丙氨酸-脯氨酸-甘氨酸）血管紧张素II的浓度-反应曲线右移，pA2值为6.0。相反，血管紧张素受体2亚型拮抗剂PD 123177和CGP 42112A并未改变对（丙氨酸-脯氨酸-甘氨酸）血管紧张素II的收缩反应。这些拮抗剂均不能改变对去甲肾上腺素的收缩反应。Leu8血管紧张素II（10^(-8) mol·L^(-1)）和DuP 753（10^(-6) mol·L^(-1)）均部分抑制了蟾蜍主动脉中血管紧张素III诱导的收缩。在此制剂中，血管紧张素III的活性又低于[天冬酰胺1-缬氨酸5]血管紧张素II，其摩尔效价比为0.293。该实验室先前的研究报道，血管紧张素II可增加蟾蜍Bufo arenarum皮肤的渗透水通透性，该作用被肽拮抗剂Leu8血管紧张素II阻断。DuP 753（10^(-6)和5×10^(-6) mol·L^(-1)）显著抑制了对[天冬酰胺1-缬氨酸5]血管紧张素II（10^(-7) mol·L^(-1)）的渗透反应，而该反应未被浓度高10倍的PD 123177或CGP 42112A抑制。DuP 753（10^(-6) mol·L^(-1)）也抑制了对血管紧张素III（10^(-7) mol·L^(-1)）的渗透反应。这些结果表明，分离的蟾蜍主动脉和皮肤中存在的血管紧张素II受体表现出与哺乳动物组织中被鉴定为血管紧张素1亚型的受体相似的药理学特征。
