Improvement in Angiotensin 1-7 precedes and correlates with improvement in Arterial stiffness and endothelial function following Renin-Angiotensin system inhibition in type 2 diabetes with newly diagnosed hypertension

Abstract Background and aim Studies in cell cultures and animal models have revealed the possible pathophysiological factors associated with vascular endothelial dysfunction. However, the same in human subjects has not been clearly established. The current study uses a novel approach to identify the factors associated with endothelial function and arterial function by altering these vascular parameters using Angiotensin-Converting-Enzyme (ACE) inhibition. Methods Diabetic patients with newly diagnosed hypertension (n = 60) were recruited for the study. Flow-mediated-dilation (FMD), carotid-femoral (cf), carotid-radial (cr) Pulse-wave-velocity (PWV), Augmentation-Index, Carotid-Intima-Media-Thickness (CIMT), serum levels of Renin, Angiotensin II (AngII), Angiotensin-Converting-Enzyme2 (ACE2), Angiotensin1-7 (Ang1-7), E-selectin, Vascular-Cell-Adhesion-Molecule-1 (VCAM-1), Highly-sensitive-C-Reactive-Protein (hsCRP) and Interleukin-10 were measured at baseline (V1), after 1 week (V2) and 3 months (V3) of ACE inhibition in patients of diabetes with newly diagnosed hypertension. The amplitude of change after 1 week (V2–V1) and 3 months (V3–V1) for the clinical and various parameters were correlated with the change in endothelial function and arterial stiffness. Results Carotid radial-PWVV2-V1 (p = 0.001) and Ang1-7V2–V1 (p = 0.01) emerged as independent predictors of FMDV2-V1. ReninV2-V1 and VCAM-1V2–V1 independently predicted E-selectinV2-V1 [(p = 0.01) and (p = 0.001), respectively]. ACE 2V2–V1 was the only independent predictor of cf-PWVV2-V1. The same parameters remained as independent predictors of the respective vascular factors after 3 months of ACE inhibition. Conclusion The study highlights the role of AngII/Ang1-7 balance in alteration of endothelial function and central arterial stiffness in humans in addition to identifying the interrelationship between the renin-angiotensin-aldosterone-system components and clinically ascertainable parameters.