Characterization of glomerular permeability and proteinuria in acute hypertension in the rat

Abstract

The effects of acute angiotensin II (AII) induced hypertension on renal hemodynamics, urinary excretory rates, and clearances of endogenous proteins, together with colloidal iron staining and numerical density of differently charged ferritins in glomerular basement membrane (GBM) have been studied. AII decreases para-aminohippurate clearance (63%) more than glomerular filtration rate (GFR) (42%), resulting in an increased filtration fraction (54%). Simultaneously, large increments in the excretory rates and clearances of albumin and IgG2a occur. The number of native ferritin particles per unit volume of GBM and its different layers increases significantly in both superficial and juxtamedullary glomeruli as a result of acute hypertension. In contrast, the number of cationized ferritin particles per unit volume of GBM as well as colloidal iron staining of GBM and adjacent cell membranes remain unchanged, irrespective of AII treatment. The results demonstrate that acute AII-induced hypertension enhances glomerular permeability to proteins of different size and shape in the absence of detectable alterations in the fixed negative charges of the GBM. Since both RBF and GFR are decreased, the increased transglomerular passage of proteins in acute hypertension appears to be due to an increase in the pore size of the glomerular filter, induced possibly by either high intracapillary pressure and/or a direct action of AII on GBM constituents.