Increased plasma endothelin-1 in pulmonary hypertension: Marker or mediator of disease?

Article Abstract:

Pulmonary hypertension is a disease in which the arteries of the lungs are subjected to much higher pressures than normal, resulting in serious damage to both the lungs and the heart, and often culminating in death. Pulmonary hypertension can be primary, with no discernible cause, or secondary, resulting from lung disease, heart disease, or lodging of blood clots in the lungs. The protein endothelin-1 has recently been identified in the bloodstream. This protein has the ability to cause the arteries of the lungs to constrict, which raises the pressure, and also causes increased growth of some of the cells that line the pulmonary blood vessels; this results in the narrowing of these vessels. A study was conducted on a total of 26 patients with pulmonary hypertension to determine if their levels of endothelin-1 were elevated, in an attempt to determine whether endothelin-1 might play an important role in pulmonary hypertension. Elevated levels of endothelin-1 were found in most patients with pulmonary hypertension, but because these levels were generally too low to cause damage to the blood vessels of the lungs, it is not clear if these elevated levels caused or resulted from damaged blood vessels in the lungs. Patients with primary pulmonary hypertension generally had the highest levels of endothelin-1, which suggests that the damaged blood vessels associated with primary pulmonary hypertension might cause these higher levels. Thus, even though the levels of endothelin-1 may be insufficient to cause the damage, their measurement might serve as a gauge of the severity of the disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

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Expression of endothelin-1 in the lungs of patients with pulmonary hypertension

Article Abstract:

Endothelin-1 may contribute to the development of several lung diseases, including pulmonary hypertension. Pulmonary hypertension is characterized by increasing resistance to blood flow in the pulmonary arteries and veins. Endothelin-1 is a substance produced by the lining of the blood vessels (the endothelium) that causes blood vessels to constrict. Samples of lung tissue were taken from 28 patients with pulmonary hypertension and 15 healthy people (the controls). Various tests were performed on the samples to detect endothelin-1 and its messenger RNA (mRNA). Microscopic examination of samples from the patients with pulmonary hypertension revealed that their arteries were thickened. Substantial amounts of endothelin-1 were found in these thickened arteries, while the control samples lacked endothelin-1. Endothelin-1 mRNA was also found in the patients' samples, but not in the control samples.

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Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension

Article Abstract:

Patients with pulmonary hypertension may have decreased production of nitric oxide synthase in the cells lining their blood vessels. Nitric oxide synthase is an enzyme that produces nitric oxide, which relaxes blood vessels and prevents the growth of the muscles lining blood vessels. Researchers analyzed the production of nitric oxide synthase in lung tissue of 22 patients with plexogenic pulmonary arteriopathy, 24 patients with pulmonary hypertension, and 23 patients with inflamed or normal lungs. The production of nitric oxide synthase was high in cells lining the normal lungs and their blood vessels. The production of the enzyme was low in lung blood vessels of patients with plexogenic pulmonary arteriopathy or pulmonary hypertension. Lower production of the enzyme was associated with blood vessels with high vascular resistance.

Enzymes

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