Muscle hypertrophy following blood flow-restricted low force isometric electrical stimulation in rat tibialis anterior: Role for muscle hypoxia

• Published in: Journal of applied physiology (1985) 2018-07, Vol.125 (1), p.134-145
• Main Authors: Nakajima, Toshiaki, Koide, Seiichiro, Yasuda, Tomohiro, Hasegawa, Takaaki, Yamasoba, Tatsuya, Obi, Syotaro, Toyoda, Shigeru, Nakamura, Fumitaka, Inoue, Teruo, Poole, David C, Kano, Yutaka
• Format: Article
• Language: English
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00972.2017

Low force exercise training with blood flow restriction (BFR) elicits muscle hypertrophy. We investigated the effects of microvascular hypoxia (i.e., low microvascular O partial pressures, PmvO ) during contractions on hypertrophic signaling, growth response and key muscle adaptations for increasing exercise capacity. Wistar rats were fitted with a cuff placed around the upper thigh and inflated to restrict limb blood flow. Low force isometric contractions (30 Hz) were evoked via electrical stimulation of the tibialis anterior (TA) nerve. The PmvO was determined by phosphorescence quenching. Rats underwent acute and chronic stimulation protocols. PmvO decreased transiently with 30 Hz contractions simultaneous BFR induced severe hypoxia reducing PmvO lower than present for maximal (100 Hz) contractions. Low force electrical stimulation (EXER) induced muscle hypertrophy (6.2%, P < 0.01) whereas CONT or BFR did not. EXER+BFR also induced an increase in muscle mass (11.0%, P < 0.01), and significantly increased fiber cross sectional area in the superficial TA (P < 0.05). Phosphorylation of ribosomal protein S6 was enhanced by EXER+BFR as PGC-1α and GLUT4 protein levels. Fibronectin type III domain-containing protein 5 (FNDC5), COX4, MCT1, and cluster of differentiation 147 (CD147) increased with EXER. EXER+BFR significantly increased MCT1 expression than EXER. These data demonstrate that microvascular hypoxia during contractions is not essential for hypertrophy. However, hypoxia induced via BFR may potentiate the muscle hypertrophic response with an increased glucose transporter and mitochondrial biogenesis, which contributes to the pleiotropic effects of exercise training with BFR that culminate in an improved capacity for sustained exercise.