title: Pentosan polysulfate prevents glomerular hypertension and structural injury despite persisting hypertension in 5/6 nephrectomy rats.
abstract: Five/six nephrectomy induces systemic and glomerular hypertension, glomerulosclerosis, proteinuria, and tubulointerstitial fibrosis. Polysulfate pentosan (PPS) decreases mesangial proliferation and extracellular matrix accumulation. The aim of this study was to determine whether PPS prevents glomerular hemodynamic changes and renal damage. Micropuncture studies were performed in three groups of eight male Wistar rats. Two groups included rats with 5/6 nephrectomy-one of which was treated with PPS in drinking water (100 mg/kg body wt) and the second of which received normal drinking water-and the third group consisted of normal rats that served as controls. Five/six nephrectomy produced systemic hypertension, a 50% reduction in GFR, and a 67% increase in single-nephron GFR due to elevated glomerular pressure and single-nephron plasma flow as well as proteinuria. Hypertension persisted in PPS-treated animals. Despite a similar reduction in GFR, PPS prevented the rise in single-nephron GFR, glomerular capillary hydrostatic pressure, and proteinuria. By morphometry, glomerular volume was increased by 46% and mesangial area by 94%. Fractional glomerular capillary area decreased by 24%. PPS prevented these changes. Tubular dilatation, epithelial cell atrophy, and increased interstitial area were largely prevented by PPS, as was the interstitial inflammatory infiltrate. These results suggest that the renal protection conferred by PPS was mediated both by prevention of glomerular hypertension as well as suppression of the inflammatory response. It was postulated that this was partly due to the preservation of a greater fraction of functional nephrons.
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Norma A
authors.initials: NA
authors.lastname: Bobadilla
authors.affiliation: Laboratory of Renal Cell Biology, Division of Nephrology, Department of Medicine, University of Miami School of Medicine, Miami, Florida.
authors.forename: Ivan
authors.initials: I
authors.lastname: Tack
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Edilia
authors.initials: E
authors.lastname: Tapia
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Laura G
authors.initials: LG
authors.lastname: Sánchez-Lozada
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Santamaría
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Jiménez
authors.affiliation: Laboratory of Renal Cell Biology, Division of Nephrology, Department of Medicine, University of Miami School of Medicine, Miami, Florida.
authors.forename: Liliane J
authors.initials: LJ
authors.lastname: Striker
authors.affiliation: Laboratory of Renal Cell Biology, Division of Nephrology, Department of Medicine, University of Miami School of Medicine, Miami, Florida.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Striker
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Jaime
authors.initials: J
authors.lastname: Herrera-Acosta
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001794:Blood Pressure; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009392:Nephrectomy / Q000379:methods*; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology*; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000925:Anticoagulants; D010426:Pentosan Sulfuric Polyester