Mesangial immune injury, hypertension, and progressive glomerular damage in Dahl rats.
Hypertension frequently accompanies chronic glomerulonephritis. Mesangial injury and glomerulosclerosis are common in glomerulonephritis and are often harbingers of progressive glomerular destruction. Thus, in a model of mesangial immune injury we studied the relationship between hypertension, mesangial injury, and glomerulosclerosis. We induced mesangial ferritin-antiferritin immune complex disease (FIC) in Dahl salt-sensitive (S) and salt-resistant (R) rats. S and R rats with FIC were fed chow containing 0.3% NaCl until 14 weeks of age and then switched to 8.0% NaCl chow until 28 weeks of age. Groups of control S and R rats (no FIC) were either fed 0.3% NaCl for 28 weeks or switched to 8.0% NaCl chow at 14 weeks of age. Blood pressure, serum creatinine, urinary protein, and glomerular injury (assessed by semiquantitative morphometric analysis) were determined at 14 and 28 weeks of age. R rats with or without FIC did not develop hypertension; mesangial injury was minimal. At 14 weeks of age, only S FIC rats developed hypertension, proteinuria, significant mesangial expansion and early glomerulosclerosis. At 28 weeks of age, proteinuria, mesangial expansion, and glomerulosclerosis were significantly more severe in hypertensive S rats with FIC than in those without FIC. These studies show that despite a normal salt intake, mesangial injury hastened the onset of hypertension, but only in rats genetically predisposed to hypertension (S FIC at 14 weeks). High dietary salt further aggravated hypertension, which, in turn, magnified both mesangial injury and glomerulosclerosis. Clinically, the different rates of progression of human glomerulonephritis associated with hypertension may be in part dependent on similar mechanisms.
D000818:Animals; D005920:Glomerular Mesangium / Q000276:immunology / Q000473:pathology*; D005921:Glomerulonephritis / Q000473:pathology*; D005923:Glomerulosclerosis, Focal Segmental / Q000276:immunology / Q000473:pathology*; D006973:Hypertension / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D007105:Immune Complex Diseases / Q000276:immunology / Q000473:pathology*; D008297:Male; D051381:Rats; D011922:Rats, Mutant Strains; D012965:Sodium Chloride / Q000008:administration & dosage
D012965:Sodium Chloride