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Investigating The Effects Of Retrograde Blood Flow In Hypertension

The endothelium, which is the inner cell layer of our vessels, is heavily associated with the maintenance of cardiovascular health. In health conditions, the endothelium is responsible for the production and release of several substances, such as nitric oxide (NO) and endothelin-1, which help keep the endothelium functioning properly.

However, in the presence of inflammation and mechanical damages to the endothelium, it becomes the site for the formation of plaques of fat and immune cells. The formation of these plaques is related to bad eating habits, lack of physical activity, and genetic factors. Over the years, these plaques grow bigger, narrowing the vessels and hardening their walls, interfering with the flow of blood through our body.

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Blood flow presents different patterns according to different body sites. For instance, in areas with branches or curvatures, or even in an area with large plaques, it can flow backwards, in what is called disturbed or retrograde blood flow. Studies have provided evidence that a retrograde blood flow pattern can lead to a phenomenon called endothelial dysfunction, characterized by the irresponsiveness of the vessel to a certain stimuli and imbalance of endothelium-derived vasoactive factors [i.e., nitric oxide (NO), endothelin-1]. The lack of vascular sensitiveness has been also associated with endothelial cell death in a process called apoptosis. The whole process is related to the development and progression of cardiovascular disease, such as heart attack, stroke, and hypertension.

Hypertension, or high blood pressure, is one of the most common heart diseases. It can start quietly, taking years until some symptom manifests itself. Uncontrolled high blood pressure can lead to severe health problems, including an improper function of the endothelium, plaque formation, and target organ diseases. The pathophysiology of hypertension is still unknown, but imbalance in NO production seems to be involved in all this process. NO is responsible for the regulation of the vessels’ caliber and vascular repair mechanisms. For example, when NO increases, it dilates the vessels; on the other hand, if there is a decrease in NO, the vessels do not dilate properly. This process implicates directly in the blood flow pattern throughout the body.

Moreover, the human organism presents mechanisms that act trying to repair all the damage inflicted in the endothelium. A group of cells from the bone marrow, called endothelial progenitor cells (EPC), is one of the responsible for restoring the health of the vessels. However, these cells are also impaired by the presence of high blood pressure and their recruitment might be damaged by the increased retrograde blood flow.

In our paper “Disturbed blood flow induces endothelial apoptosis without mobilizing repair mechanisms in hypertension”, recently published in Life Sciences we investigated the impact of different blood flow pattern on the vascular health of individuals with hypertension. For that, we manipulated the blood flow of hypertensive and health volunteers with a pressure cuff at 75mmHg. With a help of an ultrasound system, we were able to measure the responsiveness of the vessels to the procedure. Also, we collected blood samples to determine the EPC mobilization, the apoptosis level and the NO production.

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We have found that hypertension per se induces endothelial apoptosis, providing evidence that high blood pressure could lead to vascular impairment and major chances of cardiovascular events. It was observed that disturbing the blood flow reduced the capacity of vascular dilation not only in patients with hypertension but also in healthy people, which supports the idea that the presence of increased retrograde blood flow is harmful to the vessels. Individuals with hypertension also presented greater endothelial apoptosis, and reduced repair capacity, through reduced EPC mobilization and NO production.

These findings shine new light about the importance of maintenance of vascular health, defining new ways to study and understand the process behind hypertension.

These findings are described in the article entitled Disturbed blood flow induces endothelial apoptosis without mobilizing repair mechanisms in hypertension, recently published in the journal Life SciencesThis work was conducted by Helena N.M. Rocha, Vinicius P. Garcia, Gabriel M.S. Batista, Gustavo M. Silva, João D. Mattos, Monique O. Campos, Antonio C.L. Nóbrega, Igor A. Fernandes, and Natália G. Rocha from the Fluminense Federal University.

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