Microvascular Endothelial Dysfunction in Hypertension

Abstract

Endothelial dysfunction which characterizes human essential hypertension is largely dependent on an impaired endothelial nitric oxide (NO) availability and an increased production of endothelium-derived contracting factors (EDCFs), including endothelin (ET)-1, and reactive oxygen species (ROS). Acute intra-arterial administration of indomethacin, a nonselective cyclooxygenase (COX) inhibitor, and ascorbic acid, an antioxidant, normalized the blunted endothelial dysfunction by restoring NO availability at the level of peripheral microcirculation, thus demonstrating that COX-derived EDCFs are involved in generating ROS. Recent studies put in evidence new lights on the mechanisms involved in endothelial dysfunction in human hypertension. Functional and immunohistochemical experiments with selective COX inhibitors identified the isoform COX-2 as the main source of intravascular ROS generation in isolated small vessels from essential hypertensive patients. In addition, important vascular protective properties by human ghrelin have been demonstrated, in terms that its systemic reduction is involved in the pathophysiology of endothelial dysfunction, while a normalization of its levels may restore vascular homeostasis.