Renal vessel changes in diabetic KK-mice

Abstract

Glomerular hyperfiltration is thought to be of pathogenic importance in the structural abnormalities seen in diabetic nephropathy but its cause is not known. It has been suggested that the changes in the preglomerular vascular system may lead to a disturbance of glomerular blood flow in diabetes. We therefore examined the potential role of changes in the vascular system supplying the glomerulus in diabetic mice. The kidneys of 15 diabetic KK-mice (aged 2, 5 and 12 months) were studied and compared with those of 15 non-diabetic NMRI-mice. We determined vessel cross-sectional, wall and lumen areas of 408 small intrarenal arteries, 5,140 arterioles and 518 preglomerular afferent arterioles using a morphometric method. At 2 months, diabetic arteries and arterioles were considerably smaller than the controls, while preglomerular afferent arterioles were the same size. At 12 months, however, all diabetic vessels measured were much larger than the controls. This was chiefly due to an excessive increase in lumen area: in the diabetic arteries the mean (+/- SEM) lumen area at 12 months was 1,057 +/- 142 vs 616 +/- 72 sq mu in controls (P less than 0.001), in arterioles 176 +/- 7 vs 115 +/- 4 sq mu (P less than 0.001) and in preglomerular afferent arterioles (at 5 months) 131 +/- 8 vs 95 +/- 7 sq mu (P less than 0.001). The dilatation of small intrarenal arteries and arterioles in diabetic mice may result from progressive impairment of vasoconstriction and may be a cause of the glomerular hyperfiltration in diabetes.