Determinants of renal damage in rats with systemic hypertension and partial renal ablation

The mechanism responsible for the progression of renal disease to end-stage renal failure has been evaluated in different experimental models. Studies in rats with subtotal renal ablation [1], streptozotocin-induced diabetes mellitus [2], and some forms of experimental hypertension [3, 4] have suggested that increased glomerular capillary pressure and flow play a major role in the development of lesions that are ultimately responsible for the sclerosis of glomeruli and loss of kidney function. Further evidence for the role of hyperfiltration in the progression of kidney disease has been provided by the effect of dietary [1, 5] and pharmacologic manipulations [6–11], Both manipulations are effective in preventing hyperfiltration, arresting glomerular damage, and preserving morphology. The models of progressive renal damage previously mentioned share in common the presence of glomerular hypertension and glomerular hyperperfusion. Although these two alterations are present simultaneously in these models, the specific role of each one of them, that is, glomerular hypertension and hyperperfusion, is difficult to define. It is possible that each one of these hemodynamic alterations may be capable of inducing glomerular damage, or only one of them could be the critical factor. This study was designed to evaluate the role of glomerular hypertension and glomerular hyperperfusion in the development of glomerular structural damage in rats with partial ablation with and without systemic hypertension. Elevation of glomerular capillary flow was induced by partial ablation of one kidney, whereas increased glomerular capillary pressure was achieved by systemic hypertension produced by clipping the renal artery of the non-ablated kidney. Our results demonstrate that significant increases in single nephron glomerular filtration rate and blood flow alone do not produce histological changes; however, when elevated intracapillary pressure and increased glomerular volume are superimposed severe structural damage becomes apparent, suggesting that the resulting elevation of capillary wall tension may play a critical role in the development of morphological alterations in this experimental model.