Two inexpensive but widely overlooked drugs may help many patients who continue to have high blood pressure despite taking standard blood pressure medications, according to research by Indiana University School of Medicine scientists.

Howard Pratt, M.D., and his colleagues studied two compounds -- amiloride and spironolactone -- in a group of African-American patients with high blood pressure. African-Americans are disproportionately affected by high blood pressure, and tend to retain more sodium in their bodies, which is linked to high blood pressure. Amiloride and spironolactone are diuretics, or "water pills," that have been available for many years but no longer get much attention from prescribing physicians.

In the study of 98 patients, some were given one of the two drugs, some were given both, some were given a placebo. All of the patients continued to take their standard blood pressure medication. On average, blood pressures of the patients taking either amiloride or spironolactone individually, or both drugs, dropped significantly. There were no side effects. The study was published in the September issue of the journal Hypertension.

Uncontrolled blood pressure can lead to serious complications including heart attack, stroke, and kidney failure. According to some estimates, nearly one in three U.S. adults has high blood pressure.

The two drugs tested work by limiting the amount of sodium the kidneys reabsorb or take back into the body during the process of producing urine.

"The kidneys do an incredible job of holding on to sodium, which was important to the survival of our early ancestors who lived in a salt-poor world, but today there's so much salt in the food we eat that the kidneys end up holding onto too much sodium," said Dr. Pratt. The result, he said, can be high blood pressure - also known as hypertension.

The kidney retains sodium in two general regions. Traditional diuretics reduce the uptake of sodium at an early region, closer to where blood is filtered to produce urine. A region more "downstream" also takes back sodium from the urine. If too much is taken back in the first region, then the kidney adjusts by taking up less sodium in the second region. But such an adjustment doesn't always occur, with the result that the kidney ends up bringing too much sodium back into the body. This problem may worsen with age, Dr. Pratt said.

Amiloride and spironolactone work on the late or downstream region. By inhibiting the uptake of sodium there, "which is the last place in the chain of events for getting it right, you can restore blood pressure to normal levels in many patients when the drugs are used together with a standard diuretic," Dr. Pratt said.

Dr. Pratt said that physicians with patients showing resistance to treatment - patients for whom standard therapy doesn't result in a normal blood pressure - tend to prescribe higher doses of the medicine already being used, or add in a new blood pressure drug that could be expensive and often is also ineffective. He said he expects that this and additional studies will convince physicians to try the amiloride or spironolactone alternatives instead.

Dr. Pratt said the study was conducted with African-American patients because they are on average more predisposed to retain sodium, but he believes the effectiveness of the two drugs likely would be the same regardless of ethnicity.