Effects of des-aspartate-angiotensin I on angiotensin II-induced incorporation of phenylalanine and thymidine in cultured rat cardiomyocytes and aortic smooth muscle cells

Abstract

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.