19 Dec 2001

Just in time to ponder this weighty question comes a short communication in tomorrow's Nature. Martin Carrier and colleagues at the William Harvey Research Institute in London report that polyphenols in red wines potently inhibit expression of the vasoconstrictor peptide endothelin-1.

If confirmed, this finding could advance the related debates on what it is about moderate alcohol consumption that protects the heart, and whether the French paradox-despite equal saturated fat consumption, the Fois Gras have less coronary artery disease than the Roast Beefs-is a real phenomenon that is due to the French love for vin rouge.

Roger Corder et al. tested alcohol-free extracts of 23 red and four white wines, one rosé wine, as well as red grape juice on bovine aortic endothelial cells. They found that red wines reduced endothelin-1 gene expression in direct proportion to their polyphenol content, while red grape juice was only weakly active and the whites and the rosé failed to do the trick. Perhaps, though, the French should drink the competition's product: South American Cabernet was the most potent, with two microliters of extract per milliliter solution achieving a 50 percent endothelin-1 inhibition. Overall, polyphenol IC50 activity was in the 20-nanomolar range

Though polyphenols have antioxidant properties, this is probably not their modus operandi here. Instead, Corder et al. speculate that polyphenols might interfere with tyrosine kinase signaling, though this conclusion is based on only one immunocytochemistry experiment showing a redistribution of phosphotyrosine staining in cultured cells, and other literature. Red wine extract is already known to induce vasodilation and thus lower blood pressure.

What could this mean for the brain? Endothelins are normally expressed in endothelial cells of small blood vessels in the brain, and their expression is induced in reactive astrocytes (Nie XY et al., 1996). Some data suggest that Aβ enhances endothelin-1-mediated vasoconstriction (Paris et al. 1999) and that Gingko biloba exerts its purported memory-enhancing effects via endothelin-1 inhibition. Finally, recent work suggests endothelins might worsen brain damage after experimentally induced stroke in rats in part by making the blood-brain barrier more permeable (Matsuo et al., 2001).

"I would expect red wine polyphenols to inhibit endothelin-1 expression in brain endothelial cells," said Corder, though he has not studied this question. Maybe someone should? Meanwhile, all the more reason for otherwise healthy people to enjoy that glass of Cabernet guilt-free.—Gabrielle Strobel

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1. Nie XJ, Olsson Y. Endothelin peptides in brain diseases. Rev Neurosci. 1996 Jul-Sep;7(3):177-86. PubMed.
2. Paris D, Town T, Parker TA, Tan J, Humphrey J, Crawford F, Mullan M. Inhibition of Alzheimer's beta-amyloid induced vasoactivity and proinflammatory response in microglia by a cGMP-dependent mechanism. Exp Neurol. 1999 May;157(1):211-21. PubMed.
3. Matsuo Y, Mihara Si, Ninomiya M, Fujimoto M. Protective effect of endothelin type A receptor antagonist on brain edema and injury after transient middle cerebral artery occlusion in rats. Stroke. 2001 Sep;32(9):2143-8. PubMed.