EFFECTS OF DES-ASP-ANGIOTENSIN-I ON THE CONTRACTILE ACTION OF ANGIOTENSIN-II AND ANGIOTENSIN-III

Nanomolar concentrations of des-Asp-angiotensin I potentiated the contractile action of angiotensin II on the rabbit aortic ring but attenuated the contractile action of angiotensin III in the same tissue. Indomethacin had no effect on the potentiation of angiotensin II but inhibited the attenuation of angiotensin III. The action of angiotensin II, angiotensin III and des-Asp-angiotensin I was not inhibited by (S)-1-{[4-(dimethylamino)-3-methylphenyl]methyl}-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid, ditrifluoroacetate, dihydrate (PD123319), an angiotensin AT(2) receptor antagonist. The data show that angiotensin II and angiotensin III act on different subclasses of angiotensin receptors and that their actions are differentially modulated by des-Asp-angiotensin I. The data also indicate the possibility that des-Asp-angiotensin I is a functional peptide that modulates the contractile action of the two angiotensins at sub-nanomolar concentrations.