Dual renin-angiotensin system blockade and vascular remodeling

Abstract

E ssential hypertension is characterized by increased peripheral vascular resistance to blood flow particularly in younger individuals. Resistance arteries undergo vascular remodeling (reduced vascular lumen with increased media thickness) that may be functional, mechanical, and/or structural [1,2]. Small decreases in the lumen diameter significantly increase resistance to blood flow. Increased media-to-lumen ratio (M/L) is the most reproducible parameter of vascular remodeling of resistance arteries [1,3]. Interestingly, an increased M/L ratio of subcutaneous small resistance arteries is a potent predictor of cardiovascular events in patients with increased blood pressure values [4][5][6] and different cardiovascular risk [4,5]. In hypertensive patients, it is thought that increased M/L ratio could be the earliest alteration that occurs in the vasculature [7] and may precede endothelial dysfunction [7,8]. The extent of structural alterations in subcutaneous small resistance arteries is particularly pronounced in hypertensive patients with type 2 diabetes mellitus [9] or obesity [10][11][12]. Thus, the association of several cardiovascular risk factors may have a synergistic, deleterious effect on the microcirculation. Furthermore, the remodeled resistance arteries are the sites of origin of most of the wave reflections that travel backward toward the heart, contributing to the stiffness of large arteries and the increased central SBP.Despite the evidence that M/L ratio of small arteries evaluated by micromyography has a strong prognostic significance, its evaluation on a large scale, however, is limited by the local invasiveness of the assessment [13]. Therefore, the development of new, noninvasive approaches for the evaluation of microvascular damage is warranted. A promising approach for the study of microcirculation is the evaluation of the retinal vascular district, as it may be directly viewed with simple and relatively noninvasive approaches, such as the scanning laser Doppler flowmetry [13]. Recent evidence, obtained by micromyographic approaches [14] as well as by scanning laser Doppler flowmetry of retinal arteriolar vessels [15,16], suggest that presence of structural alterations of small resistance arteries may be associated with the increase in large arteries stiffness.In the study by Jumar et al.[17], arteriolar remodeling was assessed in retinal arterioles noninvasively and in vivo by scanning laser Doppler flowmetry. This is an interesting study that attempts to investigate the role of dual reninangiotensin system (RAS) blockade obtained with aliskiren on top of angiotensin receptor blockers (ARBs) on resistance arteries remodeling as well as on parameters of vascular stiffness, in hypertensive patients with no other cardiovascular risk factors. The molecular mechanisms involved in the remodeling of resistance arteries are not fully understood. Among the factors that may contribute to the structural alterations within the arterial wall, the variation of myogenic tone (ability of vessels to constri...