Reversing glomerular hypertension stabilizes established glomerular injury

Abstract

Munich-Wistar rats were studied 18 weeks following 5/6 renal ablation. In untreated group 1 rats maintained on standard chow containing 24% protein, sustained systemic and glomerular hypertension were associated with increasing proteinuria and widespread glomerular injury. In group 2, early treatment with the converting enzyme inhibitor enalapril prevented systemic and glomerular hypertension, and largely limited proteinuria and glomerular injury. Groups 3 and 4 received no therapy during the first eight weeks, during which they developed systemic hypertension and levels of proteinuria previously shown to be associated with significant glomerular sclerosis at this time point. Enalapril therapy begun at eight weeks in group 3 rats reversed systemic and glomerular hypertension, prevented a further rise in proteinuria, and limited glomerular lesions at 18 weeks relative to group 1. Reduction of dietary protein content to 12% at eight weeks in group 4 rats controlled glomerular bot not systemic hypertension to near-normal levels, stabilized proteinuria values, and also limited glomerular lesions at 18 weeks compared to group 1. These studies support the view that glomerular hypertension is an essential hemodynamic derangement responsible for progressive glomerular injury. Furthermore, reduction of capillary pressure can arrest the progression of remnant glomerular injury even when therapy is delayed until glomerular injury is established.