Physiological and Biochemical Vascular Reactivity Parameters of Angiotensin II and the Action of Biased Agonist TRV023

Abstract

Vascular reactivity experiments using isolated aortic rings have been widely used as a model for physiological and pharmacological studies since the early sixties. Here, we suggest several parameters that the researcher should pay attention to when investigating angiotensin II in their experimental models. Angiotensin II is one of the active peptides of the renin-angiotensin system and exerts its effect through the AT1 and AT2 receptors. Some studies seek to understand the effects of angiotensin II receptors at the vascular level by using vascular reactivity experiments. However, because of the large number of variations, there are only a handful of reactivity studies that seek to use this method. Thus, the objective of this study was to standardize experimental methods with angiotensin II, through vascular reactivity protocols. For this, variables such as basal tension, concentration interval, single concentration, curve concentration response, and multiple experiments using the same aortic ring were developed using the technique of vascular reactivity in an organ bath. This is the first study that has standardized the vascular reactivity protocol. In addition, we demonstrated the effects of TRV023-biased ligand of the AT1R at vascular sites.

Distinct Mechanisms of β-Arrestin–Biased Agonist and Blocker of AT1R in Preventing Aortic Aneurysm and Associated Mortality

“…88 However, β-arrestin-biased AT1R ligands did not directly cause vasoconstriction, implying that the phenomenon might be an indirect effect of 28 day exposure. 89 In summary, β-arrestin-biased AT1R agonist, TRV027 was found to inhibit AngII-induced AA in ApoE-null mice with the same efficacy as that of the ARB, OLM. The structural and dynamic properties of aorta as well as protein and DNA metabolism are better preserved by TRV027 than OLM while preventing AngII-induced remodeling of aorta.…”

“…88 However, β-arrestin–biased AT1R ligands did not directly cause vasoconstriction, implying that the phenomenon might be an indirect effect of 28 day exposure. 89…”