Reduced Repair Capacity and Endothelial Apoptosis Mediated by Retrograde Blood Flow in Hypertension
Authors: Rocha Helena Naly Miguens , Garcia Vinicius Pacheco , Silva Gabriel Matheus Batista , Lima Daniel Galinis Vieira , Silva Gustavo Mataruna , Campos Monique Opuszcka , Mattos João Dario Martins , Nóbrega Antonio Claudio Lucas , Fernandes Igor Alexandre , Rocha Natalia Galito 
Published: November 2023

Introduction

Increased retrograde blood flow has been associated with endothelial apoptosis and susceptibility to atherosclerosis. It is also stimulates the recruitment of endothelial progenitor cells (EPCs), responsible for endothelial repair and vascular remodeling, in healthy subjects. However, it is still unclear whether this mechanism is preserved in individuals at cardiovascular risk, such as hypertension.

Aim

To evaluate the effects of increased retrograde blood flow on endothelial dysfunction biomarkers in healthy individuals and patients with hypertension.

Methods

Nine normotensive subjects (CT group; 37±5 years) and four patients with hypertension (HT group; 35±2 years) were recruited. During the experimental session, two pneumatic cuffs were placed on the experimental arm for 30 minutes: (a) a distal cuff (proximal third of the forearm) inflated to 75 mmHg to produce a localized environment of retrograde blood flow in the proximal vasculature and (b) a proximal cuff (close to axilla), inflated to 40 mmHg to partially occlude venous flow from the arm, thereby facilitating the trapping of endothelial microparticles (EMPs) that were expected to be released during the experiment. Vascular reactivity was determined by brachial artery flow‐mediated dilation (FMD) at baseline and immediately after the maneuver. Blood flow measures (Ultrasound Doppler) and blood samples were obtained from both arms simultaneously (experimental and control arms) at baseline and during the last minute of the maneuver. EMPs (CD42b−/CD31+/AnnexinV+) and EPCs (CD45dim/CD34+/VEGFR2+) were measured by flow cytometry. Nitrite concentration was measured by Sievers Nitric Oxide Analyzer. This study was approved by the local ethics committee (CAAE: 36681814.3.0000.5243).

Results

At baseline, HT group presented higher levels of systolic blood pressure (SBP; p<0.05), mean blood flow (p<0.01) and EMPs (p=0.03) than CT group, while vascular conductance and FMD were similar between groups (p>0.05). Baseline EPCs was reduced in HT group (p<0.01). SBP decreased significantly during the maneuver in HT group (p=0.02). Both groups presented decreased mean blood flow (p<0.02) and vascular conductance (p≤0.01), as well as increased retrograde shear rate (p<0.01), oscillatory shear index (an indicator of the magnitude of shear oscillations; p<0.01) during the maneuver. EMP/EPC ratio was higher in HT group in both moments (p<0.02 vs. CT group). Only the HT group showed reduced FMD (p<0.01 vs. baseline) after the maneuver and increased EMP levels (p=0.02 vs. baseline) during the maneuver. EPC levels remained higher in CT group at the end of the maneuver (p<0.01 vs. HT group). There were no differences in plasma nitrite concentration. No differences were found in hemodynamic and molecular variables in the control arm.

Conclusion

These results suggest that patients with hypertension present a subclinical endothelial dysfunction along with impaired endothelial repair. Furthermore, induction of retrograde blood flow was able to augment the endothelial injury in patients with hypertension.

Support or Funding Information

Financial support: CNPq, FAPERJ, CAPES and FINEP.