Potassium initiates vasodilatation induced by a single skeletal muscle contraction in hamster cremaster muscle

Abstract

The rapid onset of vasodilatation within seconds of a single contraction suggests that the vasodilators involved may be products of skeletal muscle activation, such as potassium (K + ). To test the hypothesis that K + was in part responsible for the rapid dilatation produced by muscle contraction we stimulated four to five skeletal muscle fibres in the anaesthetized hamster cremaster preparation in situ and measured the change in diameter of arterioles at a site of overlap with the stimulated muscle fibres before and after a single contraction stimulated over a range of stimulus frequencies (4, 10, 20, 30, 40, 60 and 80 Hz; 250 ms train duration). Muscle fibres were stimulated in the absence and presence of an inhibitor of a source of K + , the voltage dependent K + channel inhibitor 3,4-diaminopyridine (DAP, 3 × 10 −4 M) and inhibitors of the K + dilatory signal transduction pathway, either a Na + K + -ATPase inhibitor (ouabain; 10 −4 M) or an inward rectifying K + channel inhibitor (barium chloride, BaCl 2 ; 5 × 10 −5 M). We observed significant inhibitions of the rapid dilatation at all stimulus frequencies with each inhibitor. The dilatory event at 4 s was significantly inhibited at all stimulus frequencies by an average of 65.7 ± 3.6%, 58.8 ± 6.1% and 64.4 ± 2.1% in the presence DAP, ouabain and BaCl 2 , respectively. These levels of inhibition did not correlate with non-specific changes in force generation by skeletal muscle measured in vitro. Therefore, our data support that K + is involved in the rapid dilatation in response to a single muscle contraction across a wide range of stimulus frequencies.

Evidence that the contraction-induced rapid hyperemia in rabbit masseter muscle is based on a mechanosensitive mechanism, not shared by cutaneous vascular beds

“…Based on different experimental models, such latency is currently reported to be "Ͻ1 s" (24,33,41,47), which is considered too short for the metabolic action to develop (11,50). However, a recent study indicates that K ϩ , released by con-tracting muscle fibers, could also mediate an early dilatory effect (2), which leaves the issue unsettled. Based on the similarity in the rapid hyperemic responses that have been reported in different preparations in response to short-lasting muscle contractions and mechanical stimuli (6,8,10,18,24,33,38,47), we hypothesized that a single mechanosensitive mechanism, activated by changes in transmural pressure, could underlie the different responses.…”

“…By administering different dilatory metabolites to isolated skeletal muscle arterioles it was shown that at least 4 s are required to elicit dilatation (50). More recently Armstrong et al (2) suggested that potassium released by the excitation of muscle fibers could play a major role in the early dilatory process, based on the observation that the dilatation (evaluated at 4 s after muscle contraction) was markedly reduced by application of various blockers of the K ϩ signaling pathway. However, these data have been questioned (9,23) on the basis of the following two facts: 1) some of the pharmacological interventions weakened the contraction of skeletal muscle fibers, thus also attenuating the mechanical action exerted on blood vessels; and 2) voltagegated K ϩ channels are also implicated in the myogenic response (15), and thus their blockade might have impaired the myogenic reactivity of the vascular network.…”

“…The rapid increase in blood flow or arteriolar diameter in response to spontaneous or stimulated contractions was investigated by several authors in both animal and human models (2,22,24,31,33,41,47). However, with a few exceptions in which skinned hindlimbs or isolated muscle preparations were investigated [e.g., Mohrman and Sparks (31)], in most studies blood flow was measured from large arteries, supplying both cutaneous and muscular vascular beds.…”

Positional differences in reactive hyperemia provide insight into initial phase of exercise hyperemia

“…Additionally, experiments measuring blood flow to the canine hindlimbs (14,15) indicate that vasodilation is necessary for the immediate hyperemia at the onset of muscle contraction. Studies published over the last decade have provided evidence for the involvement of adenosine (2), potassium (8,9), and vascular compression (6,16,37) in rapid vasodilation of the skeletal muscle resistance vasculature.…”

“…Experiments performed using the hamster cremaster (2,24) or retractor muscles (39) demonstrate that muscle contraction causes vasodilation of arterioles within 2-3 s of the onset of muscle contraction. Experiments performed in the human forearm (34,36) and dog hindlimb (26) indicate that the muscle pump cannot explain the entire hyperemic response to muscle contraction.…”