Abstract Body: It is currently accepted that angiotensin-(1-7) [Ang-(1-7)] and alamandine [Ala¹-Ang-(1-7)] are members of the counterregulatory axis of the renin-angiotensin system (RAS). Both peptides can undergo hydrolysis by angiotensin-converting enzyme and form Ang-(1-5) and Alamandine-(1-5), respectively. Recently, we have shown that Alamandine-(1-5) is present in human and mice circulation. Here, we evaluated the cardiovascular effects induced by intravenous (i.v.) administration of these peptides in conscious normotensive Wistar (n=6 for each peptide) and spontaneously hypertensive rats (SHR) (n=6 for each peptide). After a period of one hour for stabilization of the cardiovascular parameters, Alamandine-(1-5) or Ang-(1-5) were injected at a dose of 3µg/ 100g of b.w. A similar volume (0.1 ml/ 100g b.w.) of sterile saline was injected into SHR and Wistar rats for control. Alamandine-(1-5) injection produced a progressive decrease in systolic blood pressure (SBP, SHR, reaching -33±3.0 mmHg six hours after injection (Baseline SBP: 208±8 mmHg before and 175±10 mmHg, six hours after the injection). In contrast, SBP did not significantly change after the administration of Ang-(1-5) (Baseline SBP: 198±13 mmHg before and 199±8 mmHg six hours after injection). There was no significant change in heart rate (HR) in SHR after Alamandine-(1-5) (Baseline HR: 342±14 beats/min before and 341±18.8 beats/min after six hours) or after Ang-(1-5) (Baseline HR: 333±18 beats/min before and 326±19 beats/min after six hours). Alamandine-(1-5) injection in Wistar rats produced only small changes in BP (Baseline SBP: 109±10 mmHg before injection and 99±11 mmHg six hours after injection, p<0.05). No differences were observed for Ang-(1-5) injection in Wistar rats (Baseline SBP: 118±8 mmHg before injection and 115±9 mmHg six hours after injection) or in HR for Alamandine-(1-5) or Ang-(1-5). Saline injection did not change BP or HR in SHR or in Wistar rats. These results show that Alamandine-(1-5), but not Ang-(1-5), triggers a long-lasting fall in BP in hypertensive animals. These data indicate that we have identified a new vasodilatory peptide of the RAS, increasing our understanding of the complexity of this system and opening a possibility for future development of a new pharmacological target for hypertension treatment.