Effects of insulin-like growth factor-I and LR3IGF-I on regional blood flow in normal rats.
Two studies were conducted to investigate the haemodynamic effects of IGF-I and its analogue LR3IGF-I in normal anaesthetised rats. Infusion of IGF-I intravenously, at a dose of 125 micrograms/kg/h, for 20 min in the first study resulted in renal blood flow being significantly elevated by 35% above baseline. Mean arterial blood pressure (MABP) at this IGF-I dose fell by 18% of baseline, with LR3IGF-I also causing a significant decline in MABP (by 15%) at the dose of 125 micrograms/kg/h. In the second study the intravenous administration of IGF-I or LR3IGF-I, at a dose of 125 micrograms/kg/h, over a period of 60 min, resulted in MABP being significantly lowered by 25% of baseline values. Regional blood flow rates were determined using radioactive microspheres, 15 microns in diameter, injected systemically at the end of the peptide infusion period. The gastrocnemius, a representative skeletal muscle, was the only vascular region to show a significant increase in blood flow after IGF-I (by 58%) or LR3IGF-1 (by 308%) infusion. Vascular resistance in the brain was significantly reduced after infusion of IGF-I (by 60%) or LR3IGF-I (by 48%) as compared with vehicle. Skeletal muscle vascular resistance was also reduced by IGF-I (by 41%) and more particularly by LR3IGF-I (by 77%) in comparison to vehicle. These alterations to vascular tone produced by IGF infusion may be related to the central nervous system and systemic cardiovascular side-effects that have been reported during IGF-I administration in humans.
Gillespie
C M
CM
Cooperative Research Centre for Tissue Growth and Repair at the Child Health Research Institute, North Adelaide, South Australia, Australia.
Merkel
A L
AL
Martin
A A
AA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D007334:Insulin-Like Growth Factor I / Q000031:analogs & derivatives / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D007334:Insulin-Like Growth Factor I