Protective effects of flavonoids contained in the red vine leaf on venular endothelium against the attack of activated blood components in vitro.
New methods are described that allow the selective isolation of venular endothelial cells and their cultivation on porous filters to confluent monolayers. These filters with the attached endothelial cell layer can be mounted in a specially adapted apparatus allowing not only blood filtration studies, but now also the continuous registration of hydraulic conductivity (Lp) of tissue layers. This preparation responds dramatically to certain release products from simultaneously activated blood platelets and polymorphonuclear granulocytes (PMN) with a rise in Lp that, in situ, would lead rapidly to local oedema, arteriolar constriction and venular thrombosis. Selectively activated PMN alone induced only a modest increase in endothelial Lp that could be prevented by uric acid, an antioxidant. ASA prevented the activation of the blood cells, but not the effect of the release products per se, implying that the release products are probably eicosanoids. A standardized extract from red vine leaves (AS 195, active ingredient of Antistax Venenkapseln), containing in particular the flavonoids quercetin-3-O-beta-D-glucuronide and isoquercitrin (quercetin-3-O-beta-D-glucoside), not only prevented the deleterious effect of the release products on the venular endothelial monolayers but, applied promptly to an endothelium damaged by prior exposure to these release products, resulted in the repair of the endothelium. These findings identify for the first time the venular endothelium as a possible important therapeutic target in certain vascular diseases, chronic venous insufficiency being perhaps the most prominent example.
Nees
Stephan
S
Department of Physiology, Ludwig-Maximilians-Universität, Munich, Germany. stephan.nees@physiol.med.uni-muenchen.de
Weiss
Dominik R
DR
Reichenbach-Klinke
Ekkehard
E
Rampp
Florian
F
Heilmeier
Bernhard
B
Kanbach
Jürgen
J
Esperester
Anke
A
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D002196:Capillaries / Q000502:physiology; D002478:Cells, Cultured; D003470:Culture Media; D010450:Endopeptidases / Q000737:chemistry; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005374:Filtration; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D009206:Myocardium / Q000166:cytology; D009504:Neutrophils / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D010949:Plasma; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D012501:Saphenous Vein / Q000187:drug effects
D003470:Culture Media; D005419:Flavonoids; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D010450:Endopeptidases