Min L, Sim M K, Xu X G
Department of Pharmacology, Faculty of Medicine, National University of Singapore, 119260, Singapore, Singapore.
Regul Pept. 2000 Nov 24;95(1-3):93-7. doi: 10.1016/s0167-0115(00)00162-2.
Des-aspartate-angiotensin I, a pharmacologically active nine-amino acid angiotensin peptide, and losartan, an AT(1) angiotensin receptor antagonist, but not angiotensin-(1-7), another active angiotensin peptide, completely attenuated the angiotensin II-induced incorporation of [3H]phenylalanine in cultured rat cardiomyocytes. The attenuation by des-aspartate-angiotensin I but not that of losartan was inhibited by indomethacin. The data support an earlier suggestion that the nonapeptide attenuates cardiac hypertrophy in rats via an indomethacin-sensitive angiotensin AT(1) receptor subtype. In rat aortic smooth muscle cells, both des-aspartate-angiotensin I and angiotensin-(1-7) had no effect on the angiotensin II-induced [3H]phenylalanine incorporation. However, the two peptides significantly attenuated the angiotensin II-induced [3H]thymidine incorporation in the smooth muscle cells. The attenuation by angiotensin-(1-7) but not by des-aspartate-angiotensin I was inhibited by (D-Ala(7))-angiotensin-(1-7), a specific angiotensin-(1-7) antagonist. Des-aspartate-angiotensin I also attenuated FCS-stimulated [3H]thymidine incorporation. This attenuation was inhibited by the peptide angiotensin receptor antagonist, (Sar(1), Ile(8))-angiotensin II, but not by losartan. These data indicate that des-aspartate-angiotensin I and angiotensin-(1-7) do not participate in the process of protein synthesis in vascular smooth muscle cells and that the nonapeptide and heptapeptide act on different non-AT(1) receptors to mediate their anti-hyperplasic action. Although the exact mechanisms of action remain to be elucidated, the findings indicate that des-aspartate-angiotensin I acts as an agonist on angiotensin AT(1) and non-AT(1) receptor subtypes and induces responses that oppose the actions of angiotensin II.
脱天冬氨酸血管紧张素I是一种具有药理活性的九氨基酸血管紧张素肽，氯沙坦是一种AT(1)血管紧张素受体拮抗剂，而另一种活性血管紧张素肽血管紧张素-(1-7)则不能，它们能完全减弱血管紧张素II诱导的[3H]苯丙氨酸在培养的大鼠心肌细胞中的掺入。脱天冬氨酸血管紧张素I的减弱作用而非氯沙坦的减弱作用被吲哚美辛抑制。这些数据支持了早期的一个观点，即该九肽通过一种对吲哚美辛敏感的血管紧张素AT(1)受体亚型减轻大鼠的心脏肥大。在大鼠主动脉平滑肌细胞中，脱天冬氨酸血管紧张素I和血管紧张素-(1-7)对血管紧张素II诱导的[3H]苯丙氨酸掺入均无影响。然而，这两种肽显著减弱了血管紧张素II诱导的平滑肌细胞中[3H]胸腺嘧啶核苷的掺入。血管紧张素-(1-7)而非脱天冬氨酸血管紧张素I的减弱作用被特异性血管紧张素-(1-7)拮抗剂(D-Ala(7))-血管紧张素-(1-7)抑制。脱天冬氨酸血管紧张素I也减弱了胎牛血清刺激的[3H]胸腺嘧啶核苷掺入。这种减弱作用被肽类血管紧张素受体拮抗剂(Sar(1), Ile(8))-血管紧张素II抑制，但未被氯沙坦抑制。这些数据表明，脱天冬氨酸血管紧张素I和血管紧张素-(1-7)不参与血管平滑肌细胞中的蛋白质合成过程，且该九肽和七肽作用于不同的非AT(1)受体以介导其抗增殖作用。尽管确切的作用机制仍有待阐明，但这些发现表明脱天冬氨酸血管紧张素I作为血管紧张素AT(1)和非AT(1)受体亚型的激动剂，诱导与血管紧张素II作用相反的反应。
