Alpha adrenergic receptor blockade increases capillarization 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.

Esmolol acutely alters oxygen supply-demand balance in exercising muscles of healthy humans

“…Future studies could assess the effects of acute BP lowering per se (via alpha‐adrenergic blockade; see (Mortensen et al. ) on individual muscle NIRS responses to more thoroughly test this hypothesis.…”

“…3), and our use of an effective dose/selective b 1 -blocker (without peripheral vascular effects) strongly support a cause-effect relationship between acute lowering of cardiac pump function and augmented O 2 extraction in the active leg muscles. Future studies could assess the effects of acute BP lowering per se (via alpha-adrenergic blockade; see (Mortensen et al 2017) on individual muscle NIRS responses to more thoroughly test this hypothesis.…”

ExActa HIF prolyl hydroxylase inhibitors—The new lifestyle drug?

“…In illicit private use, possible overdosing cannot be prevented. It is still unknown how hypoxia/PHDi use influences the long‐term mitochondrial function or muscle capillarization . Therefore, clinicians will have to take PHDi misuse into account when unexplained high haematocrits are detected as the latter has many unfavourable effects on arterial wall properties and haemostasis …”

“…It is still unknown how hypoxia/PHDi use influences the longterm mitochondrial function or muscle capillarization. 27 Therefore, clinicians will have to take PHDi misuse into account when unexplained high haematocrits are detected as the latter has many unfavourable effects on arterial wall properties and haemostasis. 28 In conclusion, the new 'wonder drug' PHDis have the potential to replace recombinant Epo in anaemia treatment in a multitude of (pathologic) conditions and thereby improve the individual's quality of life.…”

Metabolism, obesity and the metabolic syndrome

“…Recent insights into the physiology of muscle metabolism may have implications for angiotherapeutic approaches, for example in peripheral arterial disease (PAD). Mortensen et al found that daily pharmacological treatment with an α‐adrenergic receptor blocker induced vascular proliferation in human skeletal muscle, likely due to an increase in shear stress. The increase in capillarization was associated with an increased fractional O 2 extraction, a lower blood flow and lower venous lactate levels in an exercising leg.…”