Regulation of glomerular volume in normal and partially nephrectomized rats

Abstract

Glomerular extracellular matrix accumulation may derive from the stretching of mesangial cells caused by excessive glomerular dilatation. The relationship of glomerular volume (VG) to intraglomerular pressure, expressed as compliance or as mean VG in the isolated, perfused rat glomerulus, was used to analyze factors that regulate VG. Glomeruli were highly distensible over the normal and relevant abnormal range of pressure. Compliance increased directly with basal VG (P < 0.001), i.e., larger glomeruli dilated more than smaller ones at any given pressure. Perfusion with atrial natriuretic peptide did not alter compliance, and inhibitors of nitric oxide synthesis exerted only a trivial effect. VG expansion was consistently reduced by angiotensin II, but this effect was small (3.8%, P < 0.001). After subtotal nephrectomy, compliance increased by 59% in the remnant glomeruli (P < 0.001); 22% of this increase was attributable to structural changes, and the remainder was attributable to the large basal VG of the hypertrophied glomeruli. Thus the major determinants of VG expansion include capillary wall tension, basal VG, and intrinsic distensibility, which is markedly influenced by the character of the extracellular matrix and only slightly altered by an angiotensin II-modified mesangial cell tone.

Lack of Collagen XVIII Long Isoforms Affects Kidney Podocytes, whereas the Short Form Is Needed in the Proximal Tubular Basement Membrane

“…The mechanical environment is known to have dramatic effects on cell behavior in podocytes (51) and in other situations (52). At this time, we cannot separate the mechanical characteristics of the whole glomerulus from those of the GBM, but the Col18a1 Ϫ/Ϫ glomeruli are clearly softer than normal and to a degree that is physiologically significant (28,53).…”

Mechanical Stretch Induces Monocyte Chemoattractant Activity via an NF-κB-Dependent Monocyte Chemoattractant Protein-1-Mediated Pathway in Human Mesangial Cells

“…Rises in intraglomerular pressure as measured in experimental diabetes and remnant kidney models can be calculated to result in an expansion in glomerular volume, which entails approximately a 10% radial elongation (48,49). Application of this degree of elongation to human mesangial cells in vitro resulted in a significant enhancement in MCP-1-driven monocyte recruitment.…”

Mechanical Forces in Diabetic Kidney Disease

“…Calculations suggest that the typical rise in glomerular pressure in diabetes is associated with a cell stretching of approximately 10% as compared with the average 4% elongation seen with normal intraglomerular pressure. 49, 50 We were intrigued by the hypothesis that a hemodynamic perturbation could affect the sensitivity of the cell to a metabolic stimulus and may be changing the way by which the cell "senses" the extracellular glucose level and "controls" cellular glucose uptake.…”