The effect of alpha 1 adrenoceptor antagonist prazosin on capillary supply, blood flow and performance in a rat model of chronic muscle ischaemia.
OBJECTIVE
This study explores whether the a1 blocker prazosin improves capillarisation, blood flow and muscle performance in chronically ischaemic muscles.


METHODS
Rat skeletal muscles were made ischaemic by unilateral ligation of the common iliac artery. The animals received prazosin and muscle blood flow, performance and capillary supply were studied 2 or 5 weeks later.


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 blood flow during contractions (control muscles 163 +/- 6 ml. 100 g-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 4 Hz 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 it increased C/F and blood flow.


CONCLUSIONS
Alpha1 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.
Institute of Experimental Pathology, University of Ancona, Italy.
G
G
Fulgenzi
L
L
Graciotti
M G
MG
Collis
O
O
Hudlická
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure; D002196:Capillaries / Q000187:drug effects* / Q000254:growth & development; D006652:Histological Techniques; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction; D018763:Muscle Fatigue / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D011224:Prazosin