Venous endothelial function in cardiovascular disease.

The essential role of the endothelium in vascular homeostasis is associated with the release of endothelium-dependent relaxing and contractile factors (EDRF and EDCF, respectively). Different from arteries, where these factors are widely studied, the vasoactive factors derived from the venous endothelium have been given less attention. There is evidence for a role of the nitric oxide (NO), endothelium-dependent hyperpolarization (EDH) mechanism, and cyclooxygenase (COX)-derived metabolites as EDRFs; while the EDCFs need to be better evaluated since no consensus has been reached about their identity in venous vessels. The imbalance between the synthesis, bioavailability, and/or action of EDRFs and/or EDCFs results in a pathological process known as endothelial dysfunction, which leads to reduced vasodilation and/or increased vasoconstriction. In the venous system, endothelial dysfunction is relevant since reduced venodilation may increase venous tone and decrease venous compliance, thus enhancing mean circulatory filling pressure, which maintains or modify cardiac workload contributing to the etiology of cardiovascular diseases. Interestingly, some alterations in venous function appear at the early stages (or even before) the establishment of these diseases. However, if the venous endothelium dysfunction is involved in these alterations is not yet fully understood and requires further studies. In this sense, the present study aims to review the current knowledge on venous endothelial function and dysfunction, and the general state of the venous tone in two important cardiovascular diseases of high incidence and morbimortality worldwide: hypertension and heart failure.

Protective effects of luteolin on the venous endothelium.

Luteolin is a flavonoid with antioxidant properties already demonstrated in studies related to inflammation, tumor, and cardiovascular processes; however, there are no available information regarding its antioxidant effects at the venous endothelial site. We investigated the effects of luteolin (10, 20, and 50 µmol/L) in cultures of rat venous endothelial cells. Nitric oxide (NO) and reactive oxygen species (ROS) were analyzed by fluorimetry; 3-nitrotyrosine (3-NT) residues were evaluated by immunofluorescence, and prostacyclin (PGI2) release was investigated by colorimetry. Intracellular NO levels were significantly enhanced after 10 min of luteolin incubation, with a parallel decrease in ROS generation. These results were accompanied by a significant reduction in the expression of 3-NT residues and enhanced PGI2 rates. Therefore, luteolin is effective in reducing ROS thereby improving NO availability in venous endothelial cells. Besides, luteolin-induced decrease in 3-NT residues may correlate with the enhancement in endothelial PGI2 bioavailability. These findings suggest the future application of this flavonoid as a protective agent by improving endothelial function in several circulatory disorders related to venous insufficiency.

Venous endothelium reactivity to Angiotensin II: A study in primary endothelial cultures of rat vena cava and portal vein.

The role of the vascular endothelium in modulating the arterial system has been widely investigated, but poorly explored at the venous site. In the present work, primary cultures of venous endothelium from rat Vena Cava (VC) and Portal Vein (PV) were established, characterized and analyzed according to their growth pattern and ability to produce nitric oxide (NO) and prostanoids (PGF2 α and PGI2), at basal state and after stimulation with Angiotensin II (Ang II, 1µmol/L). Basal NO was detected in all examined cells in culture. Pre-incubation with Ang II increased NO production in cells from VC (but not in PV cultures), through activation of both AT1 and AT2 receptors. Both cultures exhibited detectable levels of PGF2 α at resting conditions, which were similarly enhanced by Ang II. Basal PGI2 levels were higher in PV, but increased after Ang II treatment in VC, with no further effect on PV cells. We conclude that endothelial cells from VC and PV exhibit important properties and react to Ang II, probably influencing the whole circulatory system. This experimental cell model gives support to further studies concerning intracellular pathways of the venous endothelium, analyzed in separate from the vascular smooth muscle wall.