Fatal Contraction

Excitation-contraction coupling in heart, then and now. (A) Classic, common-pool theory of EC coupling. (B) Current, local-control mechanism of EC coupling. (C) Defect in EC coupling during heart dysfunction.

Researchers have found that a high-salt diet triggers subtle biochemical changes that can fatally throw off the heart's rhythm in rats with high blood pressure. The findings, reported in tomorrow's issue of Science,* suggest how untreated hypertension in people can lead to chronic heart failure.

Physicians have long thought that in a hypertensive person, the heart adapts to the stress by enlarging to pump blood more efficiently. Thinking such swelling may not be so benign, W. Jonathan Lederer and colleagues at the University of Maryland School of Medicine in Baltimore probed the mechanism by which heart muscle cells absorb calcium, which causes the heart to contract. They fed a high-salt diet to a strain of rats bred to have high blood pressure, and analyzed changes in the way calcium moves into a cell to trigger a contraction.

The researchers found that the gaps between the calcium channels and calcium receptors located just inside the cellular membrane had widened. At first, however, the rats overcame this defect by producing extra adrenaline that heightened the receptors' sensitivity to calcium. But after several weeks of steady enlargement, the damaged hearts began to contract poorly, resulting in heart failure.

Experts are impressed with the study. "What's surprising is that most of the problems seem to be in the one step between the electrical excitation of the heart and its contraction," says David Yue, a biomedical engineer at Johns Hopkins University School of Medicine in Baltimore. Such a fundamental, fatal process is likely also to occur in people, Lederer says. The message for those with high blood pressure, he says, is "Don't wait to treat it, because you're developing an irreversible defect." In the meantime, Lederer says, drug companies should aim to test agents that heighten the sensitivity of calcium receptors in hypertensive people.

* For more details, Science Online subscribers can link to the full text of the Report.

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