How to evaluate microvascular organ damage in hypertension: assessment of endothelial function

Abstract

Patients with essential hypertension are characterized by endothelial dysfunction and impaired nitric oxide availability secondary to oxidative stress production. A dysfunctioning endothelium is an early marker of the development of atherosclerotic changes and can also contribute to cardiovascular events. The autocrine/paracrine activity of endothelial cells makes it very difficult to investigate endothelial function in clinical research. Vascular reactivity tests represent the most widely used methods of clinical assessment of endothelial function. The aim of these tests is to activate or block endothelial cell function while measuring consequent changes in vascular tone in selected vascular districts. Many studies have evaluated the endothelium in hypertensive patients, using different techniques. Several methodologies were developed to study microcirculation (resistance arteries and arterioles), both in coronary and peripheral vascular districts. In particular, peripheral microcirculation can be evaluated in functionally isolated vascular districts such as the peripheral muscle (usually forearm), the subcutaneous tissue, or the skin. This article focuses on the most relevant available techniques in the research on endothelial dysfunction in essential hypertension, in particular their advantages and major limitations. The coronary microcirculation can be evaluated by measuring coronary blood flow with Doppler flow wire and quantitative angiography during the intracoronary infusion of endothelial agonists. The isolated and perfused forearm technique is the most often used approach in the assessment of endothelial function in peripheral muscle microcirculation. The subcutaneous small resistance arteries can be studied using the Mulvany myograph device, an in vitro, ex vivo technique. Finally, the use of the laser digital Doppler technique provides a non-invasive approach to the evaluation of the skin microcirculation. Each technique employed to assess endothelial function has specific limitations that hinder its applicability in large-scale screening. In addition, studies assessing the degree of correlation among measures of endothelial function, as evaluated in different vascular beds, have demonstrated a poor relationship and, while statistically significant, the findings are of no clinical relevance. Therefore, no one technique can be considered a surrogate for another. At the present time, the optimal methodology for investigating the multifaceted aspects of endothelial dysfunction is still under debate. Only the growing concordant results from different reproducible and reliable methods exploring endothelial function with different stimuli will support and strengthen experimental findings, thus providing conclusive answers in this area of research.