Endothelial dysfunction: methods of assessment and application to hypertension

Interest in the endothelium has been growing in recent decades and the traditional belief that it provides an inert interface between blood and the vessel wall is no longer the case. It is now clear that the endothelium produces a large number of substances that influence blood flow, and it is in turn affected by changes in the blood and the pressure of blood flow. Nitric oxide and endothelins are the major regulators of the vascular tone, and thereby the blood pressure. Historically speaking, concepts such as endothelial cell damage and injury were described in the 1960s and 1970s. More recently, terms such as endothelial cell activation and dysfunction have also been introduced. Although similar in some respects or part of a continuum, these terms differ in the actual effects on the endothelium, and hence differentiation is important. In hypertension, the delicate balance between the vasodilators and the vasoconstrictors is upset, with disturbance in the nitric oxide pathways that lead to a predominance of the vasoconstrictors. This in turn leads to many other changes that take place in the endothelium, setting up a vicious cycle that maintains the high blood pressure. Therefore, accurate assessment of vascular function is important in linking pathophysiology with clinical disease, such as hypertension. Indeed, there are several methods currently employed experimentally to assess endothelial dysfunction. However, the most widely studied and accepted tests are the estimation of plasma markers such as von Willebrand factor, E-selectin and thrombomodulin, and studies of forearm circulation in response to hypoxia induced stress ('flow mediated dilatation', FMD) or intra arterially administered drugs such as acetyl choline. The present document examines these topics. Whilst acknowledging the debt owed to animal models in the study of hypertension, we shall focus on work where primary study is in homo sapiens. A greater appreciation of how endothelial assessments are made in hypertension will have relevance for drug development and future management strategies.