3 years ago

Rapid versus slow ascending vasodilatation: intercellular conduction versus flow-mediated signalling with tetanic versus rhythmic muscle contractions.

Sinkler, Segal
In response to exercise, vasodilatation initiated within the microcirculation of skeletal muscle ascends the resistance network into upstream feed arteries (FAs) located external to the tissue. Ascending vasodilatation (AVD) is essential to reducing FA resistance that otherwise restricts blood flow into the microcirculation. We tested the hypothesis that signalling events underlying AVD vary with the intensity and duration of muscle contraction. In the gluteus maximus muscle of anaesthetized male C57BL/6 mice (age, 3-4 months), brief tetanic contraction (100 Hz, 500 ms) evoked rapid onset vasodilatation (ROV) in FAs that peaked within 4 s. In contrast, during rhythmic twitch contractions (4 Hz), slow onset vasodilatation (SOV) of FAs began after ∼10 s and plateaued within 30 s. Selectively damaging the endothelium with light-dye treatment midway between a FA and its primary arteriole eliminated ROV in the FA along with conducted vasodilatation of the FA initiated on the arteriole using ACh microiontophoresis. Superfusion of SKCa and IKCa channel blockers UCL 1684 + TRAM 34 attenuated ROV, implicating endothelial hyperpolarization as the underlying signal. Nevertheless, SOV of FAs during rhythmic contractions persisted until superfusion of NO synthase with L-NAME. Thus, ROV of FAs reflects hyperpolarization of downstream arterioles that conducts along the endothelium into proximal FAs. In contrast, SOV of FAs reflects local production of NO by the endothelium in response to luminal shear stress, which increases secondary to arteriolar dilatation downstream. Thus, AVD ensures increased oxygen delivery to active muscle fibres by reducing upstream resistance via complementary signalling pathways that reflect the intensity and duration of muscle contraction. This article is protected by copyright. All rights reserved.

Publisher URL: http://doi.org/10.1113/JP275186

DOI: 10.1113/JP275186

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