Sar1Ile7]angiotensin III, a new selective antagonist of the pressor effect of angiotensin III in conscious rats

Two analogues of angiotensin III were compared as antagonists of the pressor response to angiotensin II (ANG II) and angiotensin III (ANG III) in conscious, unrestrained rats. Dose-mean arterial pressure (MAP) response curves were obtained for ANG II and ANG III in the absence or presence of Ile7]ANG III (1.3 x 10(-7) mol/kg) or Sar1 Ile7]ANG III (1.2 x 10(-7) mol/kg). In the presence of Ile7]ANG III, the dose-MAP response curves for ANG II and ANG III were significantly displaced to the right. Ile7]ANG III behaved as a partial agonist on ANG II but not ANG III receptors. In the presence of Sar1 Ile7]ANG III, the dose-MAP response curve for ANG III but not ANG II was significantly displaced to the right. This suggests that Sar1 Ile7]ANG III is a selective antagonist of ANG III in the vasculature. Ile7]ANG III, on the other hand, antagonizes both ANG II and ANG III receptors. Our results support the hypothesis of the existence of a sub-class of angiotensin receptors activated by ANG III in the vascular smooth muscle.