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Hypertension researcher encourages colleagues to expand their focus
Date:9/14/2013

, Pollock said. He regularly reminds research colleagues that blocking angiotensin receptors won't produce nearly such dramatic results. In fact, he thinks problems with the endothelin system possibly resulting from a developmental defect or high-salt exposure early in life may help explain why some folks who eat a high-sodium diet get high blood pressure and others don't. But this leads to one of the weak points of endothelin and probably part of the reason it's not been top of mind for hypertension researchers, he said.

When the salt-eliminating B receptor is inactive for whatever reason, endothelin's A receptor, which actually constricts blood vessels, gets activated so blood pressure goes up, Pollock said. An interesting aside is that, at least in the short term, higher blood pressure makes it easier for the kidneys to eliminate sodium without the help of the B receptor.

Endothelin was labeled the most potent vasoconstrictor ever described when it was first purified in the late 1980s, but it was a long time before there was any attention paid to the diametrically opposed actions of the B receptors, Pollock said. Receptor antagonists didn't exist in those early days anyway and efforts to block endothelin synthesis didn't work well because there were so many forms of the enzyme that make endothelin scattered throughout the body, he said.

While still working for a pharmaceutical company, Pollock helped develop on one of the first A receptor antagonists that's now in the final stage of clinical trials for chronic kidney disease. Since the early patents on the endothelin-blocking drugs are about to run out, it's unlikely that new drug development dollars will be in the offing, Pollock said. The good news is that drugs already in use for pulmonary hypertension, which shut down the A receptors, likely have crossover potential for salt-sensitive hypertension, Pollock said.

Pollock's studies have shown that the kidney's endoth
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Contact: Toni Baker
tbaker@gru.edu
706-721-4421
Medical College of Georgia at Georgia Regents University
Source:Eurekalert

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