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

TY - JOUR

T1 - Alpha adrenergic receptor blockade increases capillarisation and fractional O2 extraction and lowers blood flow in contracting human skeletal muscle

AU - Mortensen, Stefan Peter

AU - Egginton, Stuart

AU - Madsen, Mads

AU - Hansen, Jonas Bo

AU - Munch, Gregers D W

AU - Iepsen, Ulrik Winning

AU - Åkerström, Thorbjörn

AU - Pedersen, Bente Klarlund

AU - Hellsten, Ylva

N1 - CURIS 2017 NEXS 106

PY - 2017/9

Y1 - 2017/9

N2 - Aim: To assess the effect of elevated basal shear stress on angiogenesis in humans and the role of enhanced skeletal muscle capillarization on blood flow and O2 extraction. Methods: Limb haemodynamics and O2 extraction were measured at rest and during one-leg knee-extensor exercise (12 and 24 W) in 10 healthy untrained young men before and after 4-week treatment with an α1 receptor-antagonist (Terazosin, 1–2 mg day−1). Corresponding biopsies were taken from the m. vastus lateralis. Results: Resting leg blood flow was increased by 57% 6 h following Terazosin treatment (P < 0.05), while basal capillary-to-fibre ratio was 1.69 ± 0.08 and increased to 1.90 ± 0.08 after treatment (P < 0.05). Leg O2 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), while leg VO2 was not different after Terazosin treatment. Conclusions: These results demonstrate that daily treatment with an α-adrenergic receptor blocker induces capillary growth in human skeletal muscle, likely due to increased shear stress. The increase in capillarization resulted in an increased fractional O2 extraction, a lower blood flow and venous lactate levels in the exercising leg. The increase in capillarization, and concomitant functional readouts in the exercising leg, may provide a basis for novel angiotherapy.

AB - Aim: To assess the effect of elevated basal shear stress on angiogenesis in humans and the role of enhanced skeletal muscle capillarization on blood flow and O2 extraction. Methods: Limb haemodynamics and O2 extraction were measured at rest and during one-leg knee-extensor exercise (12 and 24 W) in 10 healthy untrained young men before and after 4-week treatment with an α1 receptor-antagonist (Terazosin, 1–2 mg day−1). Corresponding biopsies were taken from the m. vastus lateralis. Results: Resting leg blood flow was increased by 57% 6 h following Terazosin treatment (P < 0.05), while basal capillary-to-fibre ratio was 1.69 ± 0.08 and increased to 1.90 ± 0.08 after treatment (P < 0.05). Leg O2 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), while leg VO2 was not different after Terazosin treatment. Conclusions: These results demonstrate that daily treatment with an α-adrenergic receptor blocker induces capillary growth in human skeletal muscle, likely due to increased shear stress. The increase in capillarization resulted in an increased fractional O2 extraction, a lower blood flow and venous lactate levels in the exercising leg. The increase in capillarization, and concomitant functional readouts in the exercising leg, may provide a basis for novel angiotherapy.

KW - Capillarisation

KW - Skeletal muscle

KW - Vasodilatation

U2 - 10.1111/apha.12857

DO - 10.1111/apha.12857

M3 - Journal article

C2 - 28199786

SN - 1748-1708

VL - 221

SP - 32

EP - 43

JO - Acta Physiologica

JF - Acta Physiologica

IS - 1

ER -