INTRODUCTION: Angiotensin (Ang) A was first identified in human plasma and it differs from Ang II in Ala(1) instead of Asp(1). Here, we hypothesized that the actions of this peptide might explain, at least partially, the limited effects of AT1R antagonists 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 AT1R 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. AT1R 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, differently 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.
INTRODUCTION: Angiotensin (Ang) A was first identified in human plasma and it differs from Ang II in Ala(1) instead of Asp(1). Here, we hypothesized that the actions of this peptide might explain, at least partially, the limited effects of AT1R antagonists 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 AT1R 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. AT1R 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, differently 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.
Authors: Belthrand Habiyakare; Hiba Alsaadon; Michael L Mathai; Alan Hayes; Anthony Zulli Journal: Int J Exp Pathol Date: 2014-06-20 Impact factor: 1.925
Authors: Steven J Forrester; George W Booz; Curt D Sigmund; Thomas M Coffman; Tatsuo Kawai; Victor Rizzo; Rosario Scalia; Satoru Eguchi Journal: Physiol Rev Date: 2018-07-01 Impact factor: 37.312