Cardiovascular effects of angiotensin A: a novel peptide of the renin-angiotensin system.

Introduction: Angiotensin (Ang) A was first identified in human plasma and it differs from Ang II in Ala1 instead of Asp1. Here, we hypothesized that the actions of this peptide might explain, at least partially, the limited effects of AT 1 R antago- nists in certain cardiovascular diseases. Materials and methods: The effects of Ang A and Ang II on blood pressure (BP) and heart function were compared. Importantly, participation of AT 1 R in these effects was evaluated. Furthermore, the effects of these two peptides on ischemia/reperfusion arrhythmias and involvement of calcium in these effects were investigated. Results: Administration of increasing doses of these peptides caused elevations in BP at comparable magnitude. AT 1 R blockade completely abolished these effects. The actions of these peptides in cardiac function were quite similar although the effects of Ang A were only partially blocked by losartan. Interestingly, Ang II elicited an increase in the duration of ischemia/reperfusion arrhythmias while Ang A had no effect on cardiac rhythm during reperfusion. In accordance, dif- ferently to Ang II, Ang A did not induce any significant effect on calcium transient during baseline and ischemic stress conditions. Conclusions: These data suggest that the existence of alternative peptides of the renin-angiotensin system (RAS) might contribute to the limited effects of angiotensin receptor blockers (ARBs) in certain pathophysiological circumstances.