pore radius, A

constriction (open bars). Renal vein constriction causes an increase in filtration through large nonselective pores, which accounts for increased protein filtration. B, Effects of renal vein constriction were again examined, alone (open bars) and during administration of the AII receptor antagonist saralasin (hatched bars). Saralasin reduced volume flux through the large pores, indicating that increased endogenous AII action was largely responsible for proteinuria during renal vein constriction. (From Yoshioka and coworkers [11]; with permission.)

FIGURE 6-12 (s

Local activation of the renin-angiotensin system and production of fibrogenic cytokines in experimental chronic renal disease. In situ reverse transcriptase was performed in rats with remnant kidneys to examine the level of gene expression for angiotensinogen and transforming growth factor-beta (TGF-beta). Rats still had not developed widespread morphologic evidence of glomerular injury 24 days after subtotal nephrectomy. A, At this point in time (arrows), staining for angiotensinogen messenger RNA (mRNA) was observed along the wall of a dilated capillary loop (CL) and in an adjacent cluster of mesangial cells. B, TGF-beta mRNA was present in an identical pattern in a contiguous section (arrows). C and D, Staining for angiotensinogen (panel C and TGF-beta (panel D) is examined in kidneys from rats treated with the angiotensin receptor antagonist losartan from the time of nephrec-tomy. Administration of losartan markedly reduced expression of both factors in remnant kidneys. The findings are consistent with the hypothesis that endothelial injury is associated with increased angiotensinogen production and local activation of the renin-angiotensin system, leading to increased expression of TGF-beta and progressive glomerular fibrosis. (From Lee and coworkers [12]; with permission.)

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