Interpretation of the acetylcholine test of endothelial cell dysfunction in hypertension

BACKGROUND: In the hypertensive circulation, endothelial cells may release less nitric oxide or more endothelin-1, both powerful vasoactive substances, suggesting an attractive hypothesis for the initiation or reinforcement of hypertension. These substances, however, are not the only way that endothelial dysfunction could be involved in hypertension. In this work we examine the role of the endothelium as a diffusion barrier to vasoconstrictor substances, as a metabolic barrier and as a secretory source of paracrine hormones. REVIEW OF DATA: The evidence that endothelial cell dysfunction occurs in different forms of hypertension comes mainly from the loss of relaxation revealed by the 'acetylcholine test' in a variety of preparations. We examined the strength of this evidence in terms of the stability of the agonist, equilibrium between agonist and receptor, and variations in acetylcholine and other receptor populations on endothelial and smooth muscle cells. The range (Emax) and sensitivity (EC50) of the acetylcholine test was considered in a novel approach to determine the full range by in vitro assay. Using conscious rabbits, we showed that the vascular amplifier of resistance in the hypertensive bed can lead to misinterpretation of changes in reactivity. CONCLUSION: The question of endothelial dysfunction in hypertension as determined by the acetylcholine test is far from proven.