Acute and chronic renal effects of recombinant human TGF-beta2 in the rat.
The expression of transforming growth factor-beta (TGF-beta) correlates with the incidence of renal glomerular and interstitial injury, however, nothing is known of the effect of these proteins on renal hemodynamics. This study examines the renal hemodynamic and morphologic effects of recombinant human TGF-beta2 in normal male Sprague Dawley rats. Acute infusion of TGF-beta (1.2 microg/kg per min) induced no hemodynamic changes, except for a modest though significant fall in mean arterial pressure. Administering TGF-beta2 at varying doses (20, 100, and 400 microg/kg) for 9 wk caused modest increases in systolic BP and proteinuria and minimal tubular interstitial fibrosis, however, renal hemodynamic end points were not significantly altered. TGF-beta2 (800 microg/kg) was also administered to volume-depleted rats for 7 consecutive days. In contrast to the findings in volume-replete animals, administration of TGF-beta2 to volume-depleted rats caused a marked reduction in GFR and medullary blood flow. Histologic fibrosis of the medullary vasa recta and cortical interstitium was seen, but glomeruli were unaffected. Thus, acute and short-term chronic TGF-beta2 administration did not induce major renal changes in the volume-replete state, however, TGF-beta2 combined with volume depletion caused medullary hypoperfusion and reduced GFR.
Kelly
F J
FJ
Division of Nephrology and Hypertension, Oregon Health Sciences University, Portland, USA.
Anderson
S
S
Thompson
M M
MM
Oyama
T T
TT
Kennefick
T M
TM
Corless
C L
CL
Roman
R J
RJ
Kurtzberg
L
L
Pratt
B M
BM
Ledbetter
S R
SR
D000704:Analysis of Variance; D000818:Animals; D004232:Diuretics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005665:Furosemide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000473:pathology*; D007677:Kidney Function Tests; D017078:Laser-Doppler Flowmetry; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*
D004232:Diuretics; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D005665:Furosemide