Increased Capillary Branching Contributes to Angiotensin Type 1 Receptor Blocker (ARB)–Induced Regression of Sclerosis

Abstract

Chronic kidney disease is characterized by progressive glomerulosclerosis and tubulointerstitial fibrosis. High-dose angiotensin type 1 receptor blocker (ARB) or angiotensin-converting enzyme inhibitor can induce regression of existing glomerulosclerosis, at least in part by decreasing matrix accumulation. However, the potential mechanisms of remodeling of capillary loops remain obscure. This study aimed to determine whether capillary branching was augmented in glomeruli with ARB-induced regression of sclerosis. Three-dimensional confocal images were assessed by graph theory analysis to explore the topology of the glomerular capillary network. Compared with normal glomeruli, glomeruli of rats with progressive sclerosis were enlarged but had a significantly reduced number of capillary segments and capillary branch points and decreased complexity of the glomerular network. In contrast, in rats with regression of sclerosis induced by ARB, glomerular enlargement was due to a significantly increased number of glomerular capillary segments and capillary branch points and restored complexity of the capillary network. These data support the theory that capillary growth contributes to regression of sclerosis and is mediated at least in part by ARB-induced increased complexity and branching of capillary segments.

Mechanisms of Disease Reversal in Focal and Segmental Glomerulosclerosis

“…In contrast, in rats with regression of sclerosis induced by high dose ARB, glomerular enlargement was due not to increased matrix, but due to increased number of glomerular capillary segments and capillary branch points and restored complexity of the capillary network. 36 …”

Renal Allograft Fibrosis: Biology and Therapeutic Targets

“…Although not explored extensively in native kidneys, in a number of renal glomerular diseases, regression of glomerulosclerosis has been described during antagonism of the renin-angiotensin-and/or endothelin-1 system (354)(355)(356). However, in glomeruli, regression has usually been defined as removal of early, excess matrix and the re-establishment of glomerular capillaries and the mesangium.…”

Age-Related Renal Microvascular Changes: Evaluation by Three-Dimensional Digital Imaging of the Human Renal Microcirculation Using Virtual Microscopy

“…Recent technical advances have enabled us to reconstruct high-resolution 3D images of the renal microvasculature, which have proved useful for investigating renal damage caused by an altered microvasculature [21,22,23,24,25]. Micro-computed tomography with contrast media can successfully quantify vessel density and vascular volume and has confirmed the rarefaction of renal capillaries in eNOS −/− rat kidney [21].…”