Nitric oxide flaw found in hypertension.

Some cases of high blood pressure may be caused by a shortage of nitric oxide, a gas once thought to be toxic but now known to play a fundamental role in a variety of normal bodily functions. This is the first time that a defect in the way cells handle nitric oxide has been linked to hypertension in humans, the researchers contend.

High blood pressure is known as the "silent killer" because it can lead to heart attack and stroke. About 90 to 95 percent of people with high blood pressure suffer from essential hypertension, in which the underlying cause of the vessel-pounding pressure is unknown.

In 1990, cardiologist Julio A. Panza of the National Heart, Lung, and Blood Institute in Bethesda, Md., and his colleagues suggested that blood vessels in people with essential hypertension showed an impaired ability to dilate. The researchers knew that endothelial cells -- skin-like cells that line the blood vessels -- secrete nitric oxide and other chemicals that cause blood vessel walls to expand. Panza's team wanted to find out whether this gas, which is dissolved in the blood, plays a role in essential hypertension.

In an initial study of healthy volunteers and people with essential hypertension, Panza's team pinpointed the defect: Hypertensives have a shortage of nitric oxide in the walls of their blood vessels, a condition that may lead to chronically narrowed arteries, Panza says.

The researchers knew that endothelial cells use the amino acid L-arginine to make nitric oxide, and they wondered if people with hypertension had lower than normal levels of this precursor compound. If they supplied the L-arginine, the researchers reasoned, then the endothelial cells should crank out nitric oxide and the arteries' ability to dilate should improve.

To test that theory, the team embarked on a second study. They gave 14 people with hypertension and 12 controls with normal blood pressure an infusion of the vessel-dilating substance acetylcholine. Next, they administered L-arginine in combination with acetylcholine. In controls, the addition of L-arginine significantly boosted the vessel-dilating response to acetylcholine. In contrast, the hypertensives showed no increase in dilation when given the double infusion.

That finding suggests that for hypertensive patients, the shortage of nitric oxide is not caused by reduced availability of L-arginine, Panza says. The two studies appear in the May CIRCULATION.

More research is needed to elucidate the specific abnormality in the nitric oxide system responsible for hypertension, Panza admits. It may be that the endothelial cells fail to release nitric oxide. Alternatively, he speculates, people with hypertension may destroy nitric oxide more rapidly.

People with high concentrations of cholesterol in their blood may also have an abnormal nitric oxide system. However, Panza says these people may prove to have a defect different from that linked to hypertension. For example, a 1991 German study showed that treatment with L-arginine restored the dilating ability of blood vessels in patients with high cholesterol.

The results of such work raised the hope that L-arginine might prove beneficial in the treatment of hypertension. However, the results of Panza's study seem to dim L-arginine's promise as an antihypertensive drug, comments Thomas F. Luscher of University Hospital in Bern, Switzerland, in an accompanying editorial.

Panza's study, and others like it, may lead to therapies that fix the biochemical defect underlying essential hypertension, Luscher adds.