A novel method for comparison of arterial remodeling in hypertension: quantification of arterial trees and recognition of remodeling patterns on histological sections

Abstract

Remodeling of spatially heterogeneous arterial trees is routinely quantified on tissue sections by averaging linear dimensions, with lack of comparison between different organs and models. The impact of experimental models or hypertension treatment modalities on organ-specific vascular remodeling remains undefined. A wide variety of arterial remodeling types has been demonstrated for hypertensive models, which include differences across organs. The purpose of this study was to reassess methods for measurement of arterial remodeling and to establish a morphometric algorithm for standard and comparable quantification of vascular remodeling in hypertension in different vascular beds. We performed a novel and comprehensive morphometric analysis of terminal arteries in the brain, heart, lung, liver, kidney, spleen, stomach, intestine, skin, skeletal muscle, and adrenal glands of control and Goldblatt hypertensive rats on routinely processed tissue sections. Mean dimensions were highly variable but grouping them into sequential 5 m intervals permitted creation of reliable linear regression equations and complex profiles. Averaged arterial dimensions demonstrated seven remodeling patterns that were distinct from conventional inward-outward and hypertrophic-eutrophic definitions. Numerical modeling predicted at least twenty variants of arterial spatial conformations. Recognition of remodeling variants was not possible using averaged dimensions, their ratios, or the remodeling and growth index. To distinguish remodeling patterns, a three-dimensional modeling was established and tested. The proposed algorithm permits quantitative analysis of arterial remodeling in different organs and may be applicable for comparative studies between animal hypertensive models and in human hypertension. Arterial wall tapering is the most important factor to consider in arterial morphometry, while perfusion fixation with vessel relaxation is not necessary. Terminal arteries in organs undergo the same remodeling pattern in Goldblatt rats, except for organs with hemodynamics affected by the arterial clip. The existing remodeling nomenclature should be replaced by a numerical classification applicable to any type of arterial remodeling.\n\nAuthor summaryArterial hypertension effects modern nations and is characterised by systemic hypertensive angiopathy that affects all organs. Arterial remodeling is a main factor to be analyzed in animal models and human. Despite abundant data, there is a significant lack of comparative analysis on arterial remodeling. The data from the present study have established a novel methodological approach to assess and compare arterial remodeling in hypertension. We have developed an effective algorithm for morphometry of intra-organ arteries to standardize remodeling assessment and allow comparisons between different hypertensive models, organs and species. Our study opens the possibility to assess remodeling using conventional widely used histological tissue sections with no need for special perfusion-fixation. The method will elucidate the improvement and development of animal models of hypertension, and enhance the assessment of experimental therapeutic modalities.