The effect of alpha1 adrenoceptor antagonist prazosin on capillary supply, blood flow and performance in a rat model of chronic muscle ischaemia

Objective: This study explores whether the a, blocker prazosin improves capillarisation, blocker prazosin and muscle performance in chronically ischaemic muscles. Design: Rat skeletal muscles were made ischaemic by unilateral ligation of the common iliac artery. The animals received prazosin and muscle blood pow, performance and capillary supply were studied 2 or 5 weeks later. Materials and methods: Prazosin (50 mg/l) was given in drinking water to animals with limited or intact blood supply. Muscle isometric twitch tension and fatigue index and blood flow at rest and during contractions (estimated by radio labelled microspheres) were measured in tibialis anterior, TA, and extensor digitorum longus, EDL. Capillary supply (capillary/fibre ratio, C/F) was estimated in frozen muscle sections stained for alkaline phosphatase in TA, EDL and soleus, S. Results: Prazosin increased significantly capillary supply in ischaemic muscles after 2 and 5 weeks and bloodflow during contractions (control muscles 163+/-6 mi. 100g(-1) min(-1); ligated 2 weeks 25+/-7, ligated+prazosin 116+/-38; ligated 5 weeks 27+/-7, +prazosin 137+/-29, p<0.05 vs. ligated). Fatigue index (final/peak tension over 5 min contractions at 4Hz in %) was significantly improved by prazosin after 2 weeks (FI=69+/-3% controls, 35+/-4% ligation, 60+/-3% ligation + prazosin) and less after 5 weeks (52+/-12% ligation, 61+/-3% ligation +prazosin). In contrast, prazosin had no effect on muscle performance in normal muscles in spite of if increased C/F and bloodflow. Conclusions: Alpha, adrenoceptor blockade is an effective way for improvement of capillary supply, blood flow and muscle performance in ischaemic muscles; the effect on muscle performance is most pronounced 2 weeks after induction of ischaemia.