Role of hypertension in progressive glomerular immune injury.
The relationship between hypertension, ferritin-antiferritin mesangial immune injury (FIC), and progressive glomerular damage was studied in hypertensive (8% NaCl chow) Dahl salt-sensitive rats (DS) and in spontaneously hypertensive rats (SHR). The glomeruli of SHR are protected from the increased perfusion pressure that accompanies systemic hypertension by preglomerular vasoconstriction, while the glomeruli of hypertensive DS are not. Blood pressure, serum creatinine levels, urinary protein excretion, and glomerular injury (assessed by semiquantitative morphometric analysis) were determined in 20-week-old SHR and DS with FIC. In addition, half of a group of 20-week-old SHR with FIC were uninephrectomized and progression of glomerular injury was assessed 12 weeks later. Control rats for each of the groups did not receive FIC. Our studies showed that more extensive mesangial expansion and glomerulosclerosis developed in hypertensive DS with FIC than in rats without FIC. Glomerular injury in DS with FIC affected cortical and deep glomeruli. Similarly, hypertensive SHR with FIC had minimal damage in cortical glomeruli. In deep glomeruli of SHR, mesangial expansion was similar to that of DS, but glomerulosclerosis was absent. In SHR, a 50% reduction in renal mass, a maneuver known to decrease preglomerular vasoconstriction, resulted in mesangial expansion similar to that in DS in cortical glomeruli while deep glomeruli developed mesangial expansion as well as glomerulosclerosis. Our results suggest that when hypertension and mesangial immune injury coexist with renal vasodilatation (as occurs in DS with 2 kidneys and in SHR after uninephrectomy), they act synergistically to induce progressive glomerular damage. Similar mechanisms may be operative in hypertensive humans with glomerulonephritis and may condition the rate of progression to renal insufficiency.
Raij
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L
Azar
S
S
Keane
W F
WF
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D001485:Basement Membrane; D001794:Blood Pressure; D003404:Creatinine / Q000097:blood; D005293:Ferritins / Q000276:immunology; D005920:Glomerular Mesangium / Q000502:physiology; D006973:Hypertension / Q000150:complications*; D007105:Immune Complex Diseases / Q000097:blood / Q000150:complications*; D007678:Kidney Glomerulus / Q000276:immunology*; D007684:Kidney Tubules / Q000276:immunology; D008297:Male; D011507:Proteinuria / Q000276:immunology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains
D000936:Antigen-Antibody Complex; D005293:Ferritins; D003404:Creatinine