Hypertension is a frequent clinical accompaniment of glomerulonephritis. It has long been considered that hypertension due to its injurious effects on the renal vasculature may influence the course and/or progression of glomerulonphritis. However, the mechanisms involved at the glomerular level are not fully understood. Hence, experimental models in which glomerulonephritis is accompanied by hypertension are necessary to evaluate how these factors interact and contribute to acute and chronic glomerular damage. We propose to induce glomerular injury selectively, to either the mesangium or the peripheral capillary loop in Dahl and SHR rats. These strains have a genetic predisposition to develop hypertension which has features similar to that of human hypertension. Of particular importance for our studies, is that in these two strains of rats; a) at similar levels of systemic hypertension the hemodynamic determinants of glomerular filtration are different and b) increased dietary salt is necessary for hypertension to develop in Dahl rats but not in SHR rats. Thus, these models of hypertension will afford us the unique opportunity to evaluate sequentially the reciprocal relationship between hypertension and immune as well as non-immune injury to the glomerulus. The proposed use of morphologic techniques and their correlation to the physiologic determinants of glomerular function will allow us to accomplish these goals. These studies will contribute to the understanding of the pathophysiological events that lead to progressive glomerular destruction and renal failure.
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