Scientists at the University of Maryland Medical Center, who have been searching for the cause of high blood pressure for a decade, say they have found new evidence that the recently discovered hormone ouabain is linked to hypertension in humans.
A team of researchers, headed by Dr. John M. Hamlyn, reported yesterday that in their first clinical study of ouabain (pronounced WA-bain) they were able to demonstrate that levels of the hormone increase when blood pressure rises and decrease when blood pressure falls.
"This clinical study provides the strongest evidence yet that the hormone ouabain has a direct relationship with high blood pressure," said Dr. Mordecai P. Blaustein, chairman of physiology at the UM Medical Center, who has led UM researchers trying to close in on the cause of hypertension.
The study involved nine patients with induced hypothyroidism, an uncommon form of high blood pressure that affects 10 percent of hypertensives, and compared them with 11 subjects who had normal blood pressure.
The nine people studied by the UM team were thyroid cancer patients with otherwise normal blood pressure whose blood pressure increased temporarily because they were taken off their thyroid medicine to undergo a radioactive iodine scan to see if their cancer had spread.
According to Hamlyn, preliminary data from a continuing and much larger study involving several hundred patients at UM, in London and Italy suggest ouabain may be relevant to people who suffer from "garden variety" hypertension. Ninety percent of hypertensives are in this category.
But, more research is needed to determine exactly what role ouabain plays in causing or predicting the vast majority of hypertension cases, he said.
Other studies in both animals and humans have shown elevated levels of ouabain, but no evidence of high blood pressure, the researchers further said. This leads them to suspect ouabain elevations come first, causing hypertension, rather than the reverse.
"That suggests ouabain may be the prime mover," said Hamlyn. "We think ouabain may be the major trigger in the high blood pressure."
In more than 90 percent of hypertension cases, the cause is not yet known. But, sodium does play a major role in the disease, and for several decades, scientists have been looking for a substance in the body that regulated the pumping of sodium in and out of cells.
Last September, Blaustein and Hamlyn, in collaboration with scientists from the Upjohn Co. in Kalamazoo, Mich., reported that after an eight-year search they had isolated that substance from human plasma and, to their surprise, it turned out to be ouabain.
"We were astounded to discover that ouabain was present in the human body," Hamlyn said. "This hormone is similar to the drug digitalis that is used to treat people with heart disease. It is also the same substance that African natives had extracted from plants to make poison darts, starting bofore the 16th century."
Another important possibility arising from the UM studies is the development of specific drugs that will zero in on the cause of hypertension, but the researchers warned those new medications are "a long way down the road."
Today's vast inventory of drugs reaches only the symptoms of the disease, the researchers said. Additionally, there is a lot of guesswork involved in who gets what drug, and the drugs often have adverse side effects such as dizziness, upsets in blood sugar levels and impotence.
Between 40 and 60 million Americans are plagued by high blood pressure, a condition that is a major risk factor for heart attack, stroke, blindness and kidney failure.
Although the findings announced yesterday have not yet been published, the researchers said they were presented two weeks ago at a national endocrine meeting.
In addition, the team that first announced the discovery of ouabain 10 months ago reported in yesterday's issue of the Proceedings of the National Academy of Sciences that a major source of ouabain, a naturally occurring substance in the human body and other mammals, is the adrenal gland, which is located just above the kidneys.
The hormone was found to be present in large amounts in the adrenal glands, the researchers said. The team also discovered that ouabain was secreted by cultured adrenal gland cells, demonstrating that the body actually produces this substance.