The endothelium in hypertension: bystander, target or mediator?

SUBSTANCES RELEASED FROM THE ENDOTHELIUM: The endothelium has been recognized as a source of substances that affect circulating blood cells and also contractile function, migration and proliferation of vascular smooth muscle. Alterations in the release of substances such as nitric oxide, prostaglandins and endothelin-1 may not only mimic the hemodynamic alterations seen in hypertension, but may also be involved in the development of cardiovascular complications such as myocardial infarction, renal failure and stroke.

Alterations in endothelial function occur in experimental and human hypertension, but these changes are not uniform in different models of hypertension nor in different vascular beds. Although endothelium-dependent relaxation is generally reduced in hypertension, in particular in the cerebrovascular and renal circulation and aorta, in certain models of hypertension or vascular beds little alteration has been observed. Indeed, experimental studies suggest that most of the alterations in endothelial function in hypertension are a consequence rather than a cause of high blood pressure. This indicates that endothelial dysfunction contributes to increased peripheral vascular resistance at later stages of hypertension and most likely to the development of cardiovascular complications. Under some conditions, however, certain mediators may also be overproduced as a compensatory mechanism.

In experimental animals, endothelial dysfunction is reversible by antihypertensive therapy. In contrast, in humans with hypertension and established endothelial dysfunction, reversal of the alterations appears more difficult.

The endothelium has a strategic anatomical position that allows it to regulate the function of both vascular smooth muscle and circulating blood cells (platelets, monocytes). In hypertension several alterations in endothelial function develop as the disease progresses and become most pronounced as blood pressure rises. Endothelial dysfunction may therefore make an important contribution to the pathophysiology of hypertension and its cardiovascular complications.