Alpha adrenergic receptor blockade increases capillarisation and O2 extraction and lowers blood flow in contracting human skeletal muscle

Aim: To investigate the effect of increased basal shear stress on angiogenesis, and the role of enhanced skeletal muscle capillarisation on blood flow and oxygen extraction. Methods: Limb haemodynamics and oxygen extraction were measured at rest and during one-leg knee-extensor exercise (12 and 24W) in 10 healthy untrained young men before and after 4 weeks treatment with an α1 receptor-antagonist (Terazosin, 1-2 mg day-1). Biopsies were taken from the m. vastus lateralis. Results: Resting leg blood flow was > 6 hours following Terazosin treatment (P<0.05). Basal capillary-to-fibre ratio was 1.68±0.07 and increased to 1.89±0.08 after treatment (P<0.05). Leg oxygen extraction during knee-extensor exercise was higher (4-5% ; P<0.05), leg blood flow and venous lactate levels lower (6-7%; P<0.05) and leg VO2 similar after Terazosin treatment. Conclusion: These results demonstrate that daily treatment with an α-adrenergic receptor blocker and a consequent increase in resting blood flow induces capillary growth in human skeletal muscle, likely due to increased shear stress. The increase in capillarisation led to enhanced O2 extraction in the exercising leg, concomitant with a lower blood flow and venous lactate levels.