Emerging Insights into Glomerular Vascular Pole and Microcirculation

Abstract

The glomerular vascular pole is the gate for the afferent and efferent arterioles, mesangial cells, and a frequent location of peripolar cells with an unclear function. It has been studied in definitive detail for more than 30 years, and functionally interrogated in the context of signal transduction from the macula densa to the mesangial cells and afferent arteriolar smooth muscle cells from 10 to 20 years ago. Two recent discoveries shed additional light on the vascular pole, with possibly far-reaching implications. One, which uses novel serial section electron microscopy, reveals a shorter capillary pathway between the basins of the afferent and efferent arterioles. Such a pathway, when patent, may short-circuit the multitude of capillaries in the glomerular tuft. Notably, this shorter capillary route is enclosed within the glomerular mesangium. The second study used anti-Thy 1.1-induced mesangiolysis and intravital microscopy to unequivocally establish in vivo the long-suspected contractile function of mesangial cells, with the ability to change the geometry and curvature of glomerular capillaries. These studies led me to hypothesize existence of a glomerular perfusion rheostat, in which the shorter path periodically fluctuates between being more and less patent. This action reduces or increases blood flow through the entire glomerular capillary tuft. A corollary is that the GFR is a net product of balance between the states of capillary perfusion, and that deviations from the balanced state would increase or decrease GFR. Taken together, these studies may pave the way to a more profound understanding of glomerular microcirculation under basal conditions and in progression of glomerulopathies.

Glomerular microcirculation: Implications for diabetes, preeclampsia, and kidney injury

“…Already more than 30 years ago, Steinhausen and co‐workers noted that “intraglomerular pressure alone doesn't answer many questions about the dynamics of glomerular blood flow” 1 . The partial autonomy of glomerular capillary perfusion in contributing to glomerular filtration has been recently proposed 4 . If deemed to be correct, this additional evidence of independent regulation of glomerular microcirculation confounds the conventional model.…”

“…has been recently proposed. 4 If deemed to be correct, this additional evidence of independent regulation of glomerular microcirculation confounds the conventional model. Here, I shall briefly outline the well-known autoregulatory mechanisms involved in controlling the afferent and efferent flow-pressure contribution to GFR (extraglomerular input and output); delineate hypothetical intraglomerular mechanisms of heterogeneous blood perfusion of glomerular capillary tufts; present arguments linking the well-established autoregulatory myogenic and tubuloglomerular feedback (TGF) mechanisms with the proposed intraglomerular mechanisms for redistribution of blood flow, collectively contributing to the regulation of glomerular microcirculation.…”