Role of mesangial cell contraction in adaptation of the glomerular tuft to changes in extracellular volume

Abstract

Different chronic states of mesangial cell contraction were induced by variation of extracellular volume in Munich-Wistar rats for 6 days to study the influence of mesangial cells on the geometry of the glomerular tuft. Stereological analysis of superficial glomeruli in volume-expanded rats (VE, treated with enalapril) and volume-reduced rats (VR, treated with indomethacin) revealed a glomerular tuft volume 28.7% smaller, and a capillary luminal volume 32% smaller in VR than in VE rats. The filtration area [defined as glomerular basement membrane (GBM) area facing fenestrated endothelium] was greatly reduced in VR rats (97 +/- 16 X 10(3) micron 2 vs 137 +/- 13 x 10(3) micron 2). The surface density (Sv) of the GBM was higher by approximately 10% in VR rats primarily due to the considerable increase in Sv of the perimesangial GBM subdivision (0.189 +/- 0.01 micron 2/micron 3 vs 0.153 +/- 0.01 micron 2/micron 3), indicating a higher degree of mesangial cell contraction in these animals. Our results suggest (1) that mesangial cell contraction plays a major role in the adaptation of the glomerular tuft to variations in extracellular volume; (2) that the relevance of mesangial cell contraction for the regulation of glomerular haemodynamics appears to be small; and (3) that the reduction in filtration area, although prominent, cannot fully account for the considerable decreases in the ultrafiltration coefficient observed by others in acute and chronic studies.