Insulin-like growth factor I produces renal hyperfiltration by a kinin-mediated mechanism.
Insulin-like growth factor-I (IGF-I) infusion into rats and humans reduces renal vascular resistance and raises glomerular filtration rate (GFR) and renal plasma flow (RPF). To investigate whether kinins mediate the renal vasodilatory effects of IGF-I, we infused rats with IGF-I alone or in the presence of a B2 kinin receptor antagonist. Left kidney GFR, RPF, and kinin excretion were measured during infusion of vehicle and subsequently during 60-min infusion of IGF-I or IGF-I plus kinin antagonist. IGF-I was given as a bolus (150 micrograms/kg body wt), followed by infusion at a rate of 8.3 micrograms.kg-1 x min-1 for 60 min. The kinin antagonist was infused at a dose of 1 microgram.kg-1 x min-1 for 60 min before the start of IGF-I infusion. GFR and RPF increased significantly after IGF-I infusion was begun, from baseline levels of 1.70 +/- 0.12 and 6.21 +/- 0.34 to 2.12 +/- 0.11 and 7.91 +/- 0.29 ml/min, respectively, at 20 min (P < 0.001). This effect was maintained throughout 60 min of infusion. The increase in GFR and RPF was associated with a marked rise in urinary kinin excretion, from a baseline of 8.51 +/- 6.7 to 24.7 +/- 6.7 pg/min at 20 min and 40.3 +/- 10.4 pg/min at 40 min (P < 0.001). Pretreatment with the kinin receptor antagonist blocked the rise in GFR and RPF in response to IGF-I. These data suggest that the renal vasodilatory effect of IGF-I is mediated by kinins.
Jaffa
A A
AA
Department of Medicine, Medical University of South Carolina, Charleston.
LeRoith
D
D
Roberts
C T
CT
Rust
P F
PF
Mayfield
R K
RK
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D065168:Bradykinin Receptor Antagonists; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007705:Kinins / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D065168:Bradykinin Receptor Antagonists; D007705:Kinins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007610:Kallikreins