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

Stefan Peter Mortensen; Stuart Egginton; Mads Madsen; Jonas Bo Hansen; Gregers D W Munch; Ulrik Winning Iepsen; Thorbjörn Åkerström; Bente Klarlund Pedersen; Ylva Hellsten

doi:10.1111/apha.12857

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

Stefan Peter Mortensen, Stuart Egginton, Mads Madsen, Jonas Bo Hansen, Gregers D W Munch, Ulrik Winning Iepsen, Thorbjörn Åkerström, Bente Klarlund Pedersen, Ylva Hellsten

10 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Acta Physiologica
Vol/bind	221
Udgave nummer	1
Sider (fra-til)	32-43
Antal sider	12
ISSN	1748-1708
DOI	https://doi.org/10.1111/apha.12857
Status	Udgivet - sep. 2017

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10.1111/apha.12857

Citationsformater

@article{62653be951f8455b865d090a9895c818,

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

abstract = "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.",

keywords = "Capillarisation, Skeletal muscle, Vasodilatation",

author = "Mortensen, {Stefan Peter} and Stuart Egginton and Mads Madsen and Hansen, {Jonas Bo} and Munch, {Gregers D W} and Iepsen, {Ulrik Winning} and Thorbj{\"o}rn {\AA}kerstr{\"o}m and Pedersen, {Bente Klarlund} and Ylva Hellsten",

note = "CURIS 2017 NEXS 106",

year = "2017",

month = sep,

doi = "10.1111/apha.12857",

language = "English",

volume = "221",

pages = "32--43",

journal = "Acta Physiologica",

issn = "1748-1708",

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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 -