In 1980 Robert Furchgott published in Nature the original description of the obligatory role of the endothelium in vasodilator responses to acetylcholine [1]. Because this pioneering finding resulted in the definition of the biological role of nitric oxide and endothelins, it led to an unprecedented explosion in knowledge in the field and the definition of new, major ways of inducing cellular responses. Later it was discovered that the endothelium plays a major role not only in the regulation of vascular tone but also in other crucial aspects of vascular homeostasis, including platelet aggregation, smooth muscle cell proliferation, adhesion molecule expression, and oxygen free-radical release. Thus, it progressively became clear that most types of vascular diseases are associated with a dysfunction of endothelium-dependent regulation. Hence came the emerging concept that endothelial dysfunction is the early mechanistic pathogenetic link from classical cardiovascular risk factors (including high blood pressure, hypercholesterolemia, and diabetes mellitus) to atherosclerosis and adverse cardiovascular events.
The purpose of this review is to highlight the relationship between an abnormal endothelium and essential hypertension, one of the most important cardiovascular risk factors. Issues such as oxidative stress or impaired nitric oxide availability or increased biological activity of endothelin-1 are crucial to our understanding of why hypertensive patients can develop atherosclerotic organ damage and adverse cardiovascular events. In addition, this review clarifies the reason that endothelial dysfunction should be considered an adjunctive specific target of antihypertensive treatment. Conversely, this monograph explains that the beneficial effects of first-line therapeutic agents such as calcium antagonists are partially related to their impressive ability to restore endothelial responses and nitric oxide availability by unique effects not related to blood pressure reduction but possibly to well-documented antioxidant activity.
Finally, I would like to add a brief note about why Professor Thomas Lüscher and his coworkers are superb candidates to write a review article on endothelial dysfunction in hypertension. Apart from his well-known, impressive scientific production and established leading role in international cardiovascular medicine, some years ago Professor Lüscher, working with Professor Paul M. Vanhoutte, produced the first original work in experimental genetic and secondary hypertension, discovering the mechanisms responsible for the impaired endothelial responses in animal models. Moreover, in 1990 he first published in Circulation that patients with essential hypertension are characterized by impaired vasodilating responses to acetylcholine in the peripheral circulation [2]. This body of evidence has been the groundwork from which a generation of young scientists, including myself, came to understand the pathogenetic role of endothelial alterations in human hypertension, and it has represented the scientific background of our research activity. As a consequence, much has been done in the following years by the same Thomas Lüscher and many others in this specific field, as is clearly discussed in this monograph. However, I strongly believe that Professor Lüscher’s original work still represents the fundamental knowledge for understanding the pathogenetic role of endothelial dysfunction in hypertension.  

REFERENCES

1. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373-376.

2. Linder L, Kiowski W, Buhler FR, Lüscher TF. Indirect evidence for the release of endothelium-derived relaxing factor in the human forearm circulation in vivo: blunted response in essential hypertension. Circulation 1990;81:1762-1767.