A Mechanism by Which Obesity Contributes to Hypertension

Excess fat tissue raises blood pressure. Chronically raised blood pressure, hypertension, in turn causes tissue damage to organs throughout the body. This is one of the ways in which being overweight accelerates the progression of degenerative aging and onset of age-related diseases. Researchers here report on the investigation of one of the biochemical mechanisms by which obesity can raise blood pressure; having identified it, interfering in the mechanism is the next logical step.

With obesity comes greater risk of cardiovascular disease, high blood pressure (hypertension) and stroke, among other health problems. Small arteries in our body control blood pressure. Scientists have suspected that hypertension in obesity is related to problems in endothelial cells that line these small arteries. The reasons for this, however, have been unclear - until now.

Researchers found that a protein on the membranes surrounding endothelial cells allows calcium to enter the cells and maintains normal blood pressure. Obesity, it turns out, affects this protein, called TRPV4, within tiny subsections of the cell membrane. The researchers call these faulty subsections "pathological microdomains." Obesity, the researchers found, increases the levels of peroxynitrite-making enzymes in the microdomains containing TRPV4. Peroxynitrite silences TRPV4 and lowers calcium entry into the cells. Without the proper amount of calcium, blood pressure goes up. Targeting peroxynitrite or the enzymes that make it could be an effective way to treat and prevent high blood pressure in obesity, without the side effects that would come with trying to target TRPV4 itself.

"Historically, researchers have studied larger blood vessels that don't control blood pressure. Because of our unique techniques, we are able to study the microdomains in very small arteries that control the blood pressure. Under healthy conditions, TRPV4 at these tiny microdomains helps maintain normal blood pressure. We, for the first time, show the sequence of events that lead to a harmful microenvironment for calcium entry through TRPV4. I think the concept of pathological microdomains is going to be very important not just for obesity-related studies but for studies of other cardiovascular disorders as well."

Link: https://newsroom.uvahealth.com/2020/03/09/uva-discovers-why-obesity-causes-high-blood-pressure/

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