The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 9 No.
3 • August 2006
Beneficial Effects of the Laminar Shear Stress Response Mimicked by Procyanidin-Rich Grape Seed Extract and Hawthorn
As mentioned in the
article above, procyanidins are proanthocyanidins consisting exclusively of (epi)catechin oligomers. Grape-seed extract and hawthorn (a medicinal herb) are high in procyanidin content. In a recent paper, researchers tested the inhibitory effects of these substances on endothelin-1 (a powerful vasoconstrictor) synthesis in cultured endothelial cells. Both were equally potent as suppressors of endothelin-1 synthesis. Grape-seed extract was also shown to suppress endothelin-1 while, at the same time, inducing endothelium-dependent vasodilation; this dual effect is similar to the important beneficial response triggered by laminar shear-stress blood flow. The authors identified procyanidins as the vasoactive components in both hawthorn (used in the treatment of heart failure, including double-blind, placebo-controlled human trials) and grape-seed extract.
Heart failure (HF) is a growing problem; for one thing, large numbers of people are now surviving heart attacks and then having to deal with the resulting heart damage that, for instance, increases the risk of developing heart failure. Moreover, treatment of HF has not significantly improved survival of patients in the past thirty years. Although endothelial dysfunction is often portrayed as a simple matter of decreased nitric oxide production and release, there are other changes taking place, including, importantly, an increased vasoconstriction due to excess endothelin-1 synthesis. The researchers note that endothelin-receptor antagonists initially showed promise in HF patients, but later studies proved disappointing, probably due to the inability of endothelin antagonists to correct other components of endothelial dysfunction. Although arginine supplementation can improve endothelial function by increasing nitric oxide output, we have not seen any publications on arginine reversing endothelin-1 overproduction.
Laminar shear stress (LSS) is the frictional force exerted on the endothelial cells lining blood vessels by the flow of blood passing by but moving slowly enough that it doesn’t break up into chaotic, turbulent flow. (Blood flow speeds up when blood vessels are reduced in diameter, as happens in atherosclerosis and when blood passes a blood-vessel bifurcation point.) “Reduced LSS is likely to be a key factor underlying this change [loss of endothelial function with age], precipitated by abnormalities in cardiac function and sedentary lifestyles. … In patients with HF, the beneficial effects of regular exercise may well be due to the increasing LSS occurring during exercise.”
The researchers noted that procyanidins have effects similar to the response evoked by LSS: “Thus aortic rings suspended in organ baths release NO in the absence of LSS, and synthesis of endothelin-1 by cultured endothelial cells is inhibited, two well-described responses to LSS. Moreover, treatment of endothelial cells with a procyanidin-rich red wine extract produces morphological changes with reorganization of the cytoskeleton. This results in a pattern of phosphotyrosine staining and colocalization with F-actin which is indistinguishable from that induced by LSS. Based on these observations, we hypothesize that oligomeric procyanidins act as phytochemical inducers of the LSS response, and it is this property that helps reverse the vascular dysfunction in HF.”
The researchers also note that “the endothelium-dependent vasodilation induced by procyanidins has a clear structure-activity relationship that is optimal with oligomeric procyanidins (particularly epicatechin trimers, tetramers and pentamers), but not mimicked by epicatechin monomers or dimers and, therefore, unrelated to antioxidant properties. Inhibition of endothelin-1 synthesis exhibits a similar sensitivity.”
- Corder et al. The procyanidin-induced pseudo laminar shear stress response: a new concept for the reversal of endothelial dysfunction. Clin Sci 107:513-7 (2004). See also Corder et al. Endothelin-1 synthesis reduced by red wine. Nature 414:863-4 (2001).