Cellular Basis of Hypertension

Wenzheng Zhang, Ph.D., assistant professor, renal diseases and hypertension, Medical School

Wenzheng Zhang, Ph.D

You can thank your kidneys for handling all that salt you dumped into your body with that last order of french fries. Salt regulation is vital for maintaining a properly functioning body.

“Our body needs sodium ions to carry out various biological tasks, such as nutrient transport, nerve impulse transmission, muscle contraction and control of blood pressure,” said Wenzheng Zhang, Ph.D. “The kidney plays a dominant role in maintaining sodium balance and blood pressure, mainly through the aldosterone signal pathway.” Aldosterone is a steroid hormone secreted by the adrenal gland.

“To date, all cases of inherited hypertension result from inappropriate regulation of aldosterone or its downstream effectors,” Zhang said. Hypertension – or high blood pressure – can cause a wealth of health problems, including heart attack, stroke and kidney failure. “The treatment of hypertension costs the U.S. health system more than $13 billion per year,” he said.

The steroid aldosterone turns on the ENaC genes, which encode for proteins that form an ion channel, conveying sodium ions through the cell membrane into the cells. “Sodium ions are constantly lost through sweat and urine and replaced through the diet,” Zhang said. The sodium that is lost must be replaced by the action of ENaC ion channels, transporting new sodium ions into cells. Defects in the ENaC genes lead to Liddle’s syndrome, a rare, inherited form of saltsensitive hypertension.

Transcription of the ENaC genes – turning the genetic message into a protein ion channel – is an important point of regulation for the mechanism of hypertension.

“All organisms, ranging from fruit flies to humans, have their genes packed into a tightly wound form around a ‘scaffolding’ called chromatin,” Zhang said. Histone proteins are the building blocks of chromatin.

He has dedicated his work to understanding how chromatin regulates gene transcription. His current project specifically looks at the role of chromatin in regulation of the ENaC gene. Zhang studies how aldosterone induces changes in chromatin to facilitate ENaC transcription.

“My research in the past three years has led to a finding of a novel aldosterone signaling network that controls ENaC transcription through histone modifications,” Zhang said.

Through further research into the mechanism of ENaC transcriptional control, Zhang is helping to discover the cellular basis of hypertension.

But you should still try to cut back on those french fries.