Researchers at the University of Virginia have identified a key contributor to hypertension that could lead to new treatments with fewer side effects. Their findings were published in the journal Circulation.
The discovery, from scientist Swapnil Sonkusare, PhD, and colleagues, sheds new light on blood pressure regulation and how problems with this critical biological process drive hypertension.
Blood pressure is partly controlled by calcium levels in smooth muscle cells that line blood vessel walls. Smooth muscle cells take in calcium and use it to regulate the contraction of blood vessels as needed. Hypertension is commonly treated with calcium blockers that reduce the movement of calcium, but since multiple organs also use this calcium mechanism, these drugs have many side effects. So a treatment option that targets the harmful effects of calcium but not its beneficial effects could be very helpful for patients with hypertension.
Dr Sonkusare and his team discovered two critical signalling centres in smooth muscle cells that bring in calcium and regulate blood pressure. These ‘nanodomains’, the researchers found, act like symphony conductors for blood vessels, directing them to contract or relax as needed. These signalling centres, the researchers determined, are a key regulator of healthy blood pressure.
Further, the UVA scientists found that disruptions in this process contribute to high blood pressure. In both mouse models of the disease and hypertensive patients, the fine balance between constrictor and dilator signalling centres is lost. This caused the blood vessels to become too constricted, driving up blood pressure.
“Our work identifies a new mechanism that helps maintain healthy blood pressure and shows how abnormalities in this mechanism can lead to hypertension,” said Dr Sonkusare. “The discovery of a new mechanism for elevation of blood pressure could provide therapeutic targets for treating hypertension.”
The research identifies a “new paradigm in hypertension,” according to an accompanying editorial. The editorial says UVA’s “innovative” discoveries fill “major gaps” in our understanding of the fundamental molecular causes of high blood pressure.
The new findings help us better understand how our bodies maintain proper blood pressure and provide enticing targets for scientists seeking to develop treatments targeting underlying causes of hypertension. Developing treatments that do not affect the beneficial effects of calcium will require additional research and a deeper understanding of the calcium-use process, but Dr Sonkusare’s team is already working toward that goal.
“We’ve shown that smooth muscle cells use ‘spatial separation’ of signalling centres to achieve constriction or dilation of arteries. We are now investigating the individual components of these signalling centres,” Dr Sonkusare said. “Understanding these components will help us target them to lower or raise the blood pressure in disease conditions that show high or low blood pressure, respectively.”
Source: University of Virginia
