Shear stress-induced angiogenesis in mouse muscle is independent of the vasodilator mechanism and quickly reversible.
Is modulation of skeletal muscle capillary supply by altering blood flow due to a presumptive shear stress response per se, or dependent on the vasodilator mechanism?



The response to four different vasodilators, and cotreatment with blockers of NO and prostaglandin synthesis, was compared. Femoral artery blood flow was correlated with capillary-to-fibre ratio (C:F) and protein levels of putative angiogenic compounds.



All vasodilators induced a similar increase in blood flow after 14 days, with a similar effect on C:F (1.62 ± 0.05, 1.60 ± 0.01, 1.57 ± 0.06, 1.57 ± 0.07, respectively, all P < 0.05 vs. control 1.20 ± 0.01). Concomitant inhibitors revealed differential effects on blood flow and angiogenesis, demonstrating that a similar response may have different signalling origins. The time course of this response with the most commonly used vasodilator, prazosin, showed that blood flow increased from 0.40 mL min-1to 0.61 mL min-1by 28 days (P < 0.05), dropped within 1 week after the cessation of treatment (0.54 mL min-1; P < 0.05) and returned to control levels by 6 weeks. In parallel with FBF, capillary rarefaction began within 1 week (P < 0.05), giving C:F values similar to control by 2 weeks. Of the dominant signalling pathways, prazosin decreased muscle VEGF, but increased its cognate receptor Flk-1 (both P < 0.01); levels of eNOS varied with blood flow (P < 0.05), and Ang-1 initially increased, while its receptor Tie-2 was unchanged, with only modest changes in the antiangiogenic factor TSP-1.



Hyperaemia-induced angiogenesis, likely in response to elevated shear stress, is independent of the vasodilator involved, with a rapid induction and quick regression following the stimulus withdrawal.
School of Biomedical Sciences, University of Leeds, Leeds, UK. s.egginton@leeds.ac.uk.
S
S
Egginton
Science Department, Denefield School, Reading, UK.|Centre for Cardiovascular Sciences, Medical School, University of Birmingham, Birmingham, UK.
A
A
Hussain
Centre for Cardiovascular Sciences, Medical School, University of Birmingham, Birmingham, UK.
J
J
Hall-Jones
Centre for Cardiovascular Sciences, Medical School, University of Birmingham, Birmingham, UK.
B
B
Chaudhry
Centre for Cardiovascular Sciences, Medical School, University of Birmingham, Birmingham, UK.
F
F
Syeda
Centre for Biological Engineering, Loughborough University, Loughborough, UK.
K E
KE
Glen
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D019806:Cromakalim / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011224:Prazosin / Q000494:pharmacology; D013314:Stress, Mechanical; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D043925:Angiogenesis Inducing Agents; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019806:Cromakalim; D000431:Ethanol; D014700:Verapamil; D019001:Nitric Oxide Synthase; D011224:Prazosin; D007213:Indomethacin

EDL
; 
VEGF
; cromakalim; ethanol; prazosin; verapamil