EFFECTS OF INSULIN-LIKE GROWTH-FACTOR-I AND LR(3)IGF-I ON REGIONAL BLOOD-FLOW IN NORMAL RATS

Two studies were conducted to investigate the haemodynamic effects of IGF-I and its analogue LR(3)IGF-I in normal anaesthetised rats. Infusi on of IGF-I intravenously, at a dose of 125 mu g/kg/h, for 20 min in t he first study resulted in renal blood flow being significantly elevat ed by 35% above baseline. Mean arterial blood pressure (MABP) at this IGF-I dose fell by 18% of baseline, with LR(3)IGF-I also causing a sig nificant decline in MABP (by 15%) at the dose of 125 mu g/kg/h. In the second study the intravenous administration of IGF-I or LR(3)IGF-I, a t a dose of 125 mu g/kg/h, over a period of 60 min, resulted in MABP b eing significantly lowered by 25% of baseline values. Regional blood f low rates were determined using radioactive microspheres, 15 mu m in d iameter, injected systemically at the end of the peptide infusion peri od. The gastrocnemius, a representative skeletal muscle, was the only vascular region to shaw a significant increase in blood flow after IGF -I (by 58%) or LR(3)IGF-I (by 308%) infusion. Vascular resistance in t he brain was significantly reduced after infusion of IGF-I (by 60%) or LR(3)IGF-I (by 48%) as compared with vehicle. Skeletal muscle vascula r resistance was also reduced by IGF-I (by 41%) and more particularly by LR(3)IGF-I (by 77%) in comparison to vehicle. These alterations to vascular tone produced by IGF infusion may be related to the central n ervous system and systemic cardiovascular side-effects that have been reported during IGF-I administration in humans.