Increased glomerular capillary pressure alters glomerular cytokine expression.
Increased glomerular capillary hydrostatic pressure (PGC) is an important hemodynamic determinant of glomerular injury, but the molecular events responsible for this association are poorly understood. PGC is normal in spontaneously hypertensive rats (SHR), but uninephrectomy leads to an increase in PGC and accelerated glomerulosclerosis. Since recent studies have implicated transforming growth factor-beta 1 (TGF-beta 1) and platelet-derived growth factor sought to determine if uninephrectomy increased mRNA levels for TGF-beta 1 and PDGF in glomeruli of SHR. Since treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril lowers PGC and prevents glomerulosclerosis in uninephrectomized SHR, we also sought to determine if ACE inhibitor lowered mRNA levels for TGF-beta 1 and PDGF in the glomeruli of uninephrectomized SHR. PGC increased from 53 +/- 1 to 64 +/- 1 mm Hg 1 week after uninephrectomy in SHR (P < .05). The increase in PGC was associated with a sixfold rise in mRNA levels for TGF-beta 1 and a twofold rise in mRNA levels for PDGF in glomeruli. mRNA levels for PDGF returned to normal 2 weeks after nephrectomy, but the increase in mRNA levels for TGF-beta 1 was sustained. An increase in TGF-beta 1 immunostaining was detectable in glomeruli 4 weeks after nephrectomy. Treatment with ACE inhibitor normalized PGC (51 +/- 1 mm Hg) and prevented the rise in glomerular mRNA levels for TGF-beta 1 and PDGF. We conclude that an acute increase in PGC leads to increased TGF-beta 1 and PDGF expression in the glomerulus, thus linking changes in PGC to cytokine gene expression.
Shankland
S J
SJ
Department of Medicine, University of Toronto, Ontario, Canada.
Ly
H
H
Thai
K
K
Scholey
J W
JW
D000818:Animals; D001794:Blood Pressure; D015152:Blotting, Northern; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004656:Enalapril / Q000494:pharmacology; D015870:Gene Expression; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011918:Rats, Inbred SHR; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics
D016207:Cytokines; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004656:Enalapril