Afferent arteriolopathy and glomerular collapse but not segmental sclerosis induce tubular atrophy in old spontaneously hypertensive rats

• In chronic renal disease, the temporal and spatial relationship between vascular, glomerular and tubular changes is still unclear. Hypertension, an important cause of chronic renal failure, leads to afferent arteriolopathy, segmental glomerulosclerosis and tubular atrophy in the juxtamedullary cortex. We investigated the pathological changes of hypertensive renal disease in aged spontaneously hypertensive rats using a large number of serial sections, where we traced and analyzed afferent arteriole, glomerulus and proximal tubule of single nephrons. Our major finding was that both afferent arteriolopathy and glomerular capillary collapse were linked to tubular atrophy. Only nephrons with glomerular collapse (n = 13) showed tubules with reduced diameter indicating atrophy [21.66 +/- 2.56 mu m vs. tubules in normotensive Wistar Kyoto rats (WKY) 38.56 +/- 0.56 mu m, p < 0.05], as well as afferent arteriolar wall hypertrophy (diameter 32.74 +/- 4.72 mu m vs. afferent arterioles in WKY 19.24 +/- 0.98 mu m, p < 0.05). Nephrons with segmental sclerosis (n = 10) did not show tubular atrophy and tubular diameters were unchanged (35.60 +/- 1.43 mu m). Afferent arteriolar diameter negatively correlated with glomerular capillary volume fraction (r = -0.36) and proximal tubular diameter (r = -0.46) implying reduced glomerular and tubular flow. In line with this, chronically damaged tubules showed reduced staining for the ciliary protein inversin indicating changed ciliary signalling due to reduced urinary flow. This is the first morphological study on hypertensive renal disease making correlations between vascular, glomerular and tubular components of individual nephron units. Our data suggest that afferent arteriolopathy leads to glomerular collapse and reduced urinary flow with subsequent tubular atrophy.

Nyckelord

Spontaneously hypertensive rats

Serial sections

Focal and segmental glomerulosclerosis

Glomerular collapse

Tubular atrophy

Inversin

MEDICINE

MEDICIN

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ref (ämneskategori)

art (ämneskategori)