Atherosclerosis KOs anti-spasm fighter.

Atherosclerosis KOs anti-spasm fighter

Scientists last week reported the discovery of a machanism by which atherosclerosis may trigger high blood pressure, heart disease and stroke. The key appears to be atherosclerosis's disruption of the production of "endothelium-derived relaxing factor' (EDRF), a substance that appears to prevent constriction of blood vessels. When atherosclerosis interferes with the supply of EDRF to muscle fibers inside vessel walls, segments of the vessel may rapidly open and close in a process called vasospasm, which could then lead to heart and blood-pressure-related problems.

Normal blood flow is maintained by interactions among the clot-inducing blood cells called platelets, the endothelial cells lining the vessels and the smooth-muscle fibers running beneath the endothelium. Scientists have known for several years that platelet secretions induce the endothelium to produce EDRF, which then acts to relax underlying muscle. If the endothelium is damaged, however, this three-step balance is lost and muscle fibers constrict.

Although EDRF's identity is incomplete, researchers earlier this year identified nitric oxide as a potential EDRF candidate, and there may be other, still-unknown secreted substances that similarly relax vessels. Studies in animals are confirming its importance in maintaining cardiovascular health. Reports from the annual American Heart Association meeting in Anaheim, Calif., suggest that reduced EDRF concentrations may lead to the intermittent pain experienced by some cardiac patients, as well as other symptoms associated with vessel and blood-pressure abnormalities. The most recent studies suggest that EFRF and atherosclerosis are linked in ways that could harm the patient.

Production of EDRF is "greatly impaired' in atherosclerosis, says Donald D. Heistad of the University of Iowa in Iowa City. He says atherosclerotic lesions inside the vessel walls impede EDRF production, and vessels tend to constrict and stop blood flow to tissues--with medical consequences that may be serious. "Spasm clearly is important in [problems associated with] the heart,' says Heistad. "We suggest that it also may be important in transient ischemic attacks [minor strokes] in the brain.'

To test the effects of atherosclerosis on the EDRF-mediated process, Heistad and his co-workers studied monekeys with normal blood vessels, early atherosclerosis or advanced atherosclerosis. Those with lesions had been fed fatty diets for 18 months prior to the study. The scientists found that even minor atherosclerotic changes in vessels impaired EDRF secretion. But if monkeys were given normal diets that lowered their cholesterol, endothelial production of EDRF was restored. This, says Heistad, could mean that a switch to low-cholesterol diets actually reduces vasospasms, rather than opening narrowed vessels as originally thought.

Because endothelial damage is a common denominator in this loss of vessel "relaxation,' scientists at the meeting said that physicians evaluating a patient should consider endothelial damage caused by viruses, vessel transplantation and vessel catheterization during diagnostic testing.