Glomerular and tubular damage in normotensive and hypertensive rats

Abstract

Tubular cell damage is an important mediator of interstitial fibrosis in chronic renal diseases. Glomerular and tubular damage in genetic hypertension was therefore studied. Tubular and glomerular damage was investigated in 10-, 40-, and 70-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and compared with glomerular capillary pressure (PGC) and glomerulosclerosis in superficial (OC) and juxtamedullary (JMC). Tubular vimentin was used as criterion of tubular damage. Variation in tubular diameter was measured during change in perfusion pressure, and ureter ligation was used to demonstrate the relationship between tubular pressure and appearance of vimentin-positive cells. Tubular and glomerular damage was most pronounced in JMC and greater in SHR than in WKY. It was absent in 10-wk-old WKY and significantly higher in JMC of SHR compared with WKY at 70 wk of age. Numbers of vimentin-positive segments were 18 Ϯ 9 vs. 38 Ϯ 7% in JMC of 70-wk-old WKY and SHR (P Ͻ 0.02), and glomerulosclerosis was seen in 8 Ϯ 3 vs. 19 Ϯ 5% of glomeruli in JMC of 70-wk-old WKY and SHR, respectively (P Ͻ 0.01). P GC was 45 Ϯ 3 mmHg in JMC of WKY and 57 Ϯ 3 mmHg in JMC of 70-wk-old SHR (P Ͻ 0.001). Tubular diameter variation was greatest in SHR (P Ͻ 0.05) during pressure variation. Proteinuria was present only in 40-and 70-wk-old SHR and did not correlate with tissue damage. Tubular and glomerular damage in both strains develops in parallel and may be caused by a common mechanism, which may be glomerular capillary and tubular wall stretch during acute blood pressure variation which is greatest in JMC in SHR.vimentin; sclerosis index; glomerular capillary pressure; proteinuria IN PROGRESSIVE HYPERTENSIVE disease, physical factors such as increased glomerular capillary pressure (P GC ), filtration rate, and flow are considered to be important mediators of glomerulosclerosis (15,21). Recent research has focused on other aspects, such as growth, tubular damage, accumulation of collagens, and appearance of immune cells in the peritubular interstitium. Altered tubular cell function seems to play a pivotal role in development of the tubulointerstitial pathology (25). In diseased kidneys, tubular cells may acquire macrophage-like attributes and synthesize complement, MCH class II molecules, actin of the smooth muscle cell type, growth factors, chemokines, and other cytokines, i.e., orchestrate a chronic immune process in the peritubular interstitium and disturb the balance of growth and structure (17,20,28).It is well documented that glomerulosclerosis in hypertension is greater in the deep than in the superficial cortex (11,22), and the tubular derangement in inner cortex is also more pronounced than in the outer cortex (24). In the hypertensive animal, proteinuia develops from juxtamedullary nephrons and P GC is higher in glomeruli in juxtamedullar than superficial glomeruli in hypertensive rats (11). The early development of juxtamedullary degeneration in hypertensive animals has also been supported by a recent study w...

Arterial spin labeling blood flow magnetic resonance imaging for evaluation of renal injury

“…Interestingly, SHR were found to display significantly lower RBF in the cortex than the control group. This pathology could have been the direct result of peripheral elevation of blood pressure, since increased blood pressure in SHR rats causes the cortex injury, including glomerulosclerosis and proximal tubular damage leading to insufficient RBF autoregulation (16).…”

Treatment with pyrrolidine dithiocarbamate improves proteinuria, oxidative stress, and glomerular hypertension in overload proteinuria

“…Previous studies demonstrated that in AO rats proteinaceous casts and interstitial changes are more prevalent in the deeper regions of the cortex than in the superficial zone (14). Other workers reported increased susceptibility of juxtamedullary nephrons in the presence of proteinuria and hypertension (27). To gain some insight into the mechanism that may be involved in the discordant changes in whole GFR and SNGFR in AO rats, we quantified the presence of proteinaceous casts in renal cortex and medulla.…”

Upregulation of tissue inhibitor of metalloproteases-1 (TIMP-1) and procollagen-N-peptidase in hypertension-induced renal damage

“…At 40 weeks of age, the juxtamedullary P GC is constantly elevated while the degree of glomerulosclerosis continuously increases with age and is pronounced in 60-70-week-old rats [1]. At 40 weeks of age, significant proteinuria is seen, and it worsens with age in contrast to normotensive Wistar-kyoto rats (WKY), which demonstrate no proteinuria even though this strain exhibits juxtamedullary sclerosis with aging although less than in SHR [1,2].…”

“…The interstitium is expanded with infiltration of lymphocytes and deposition of collagen. In addition, hypertrophy and hyperplasia of the cellular components in the glomeruli associated with sclerosis are striking findings in the deep cortex of the hypertensive animals [2,3].…”