Mechanical influences on skeletal muscle vascular tone in humans: insight into contraction-induced rapid vasodilatation

Abstract

We tested the hypothesis that mechanical deformation of forearm blood vessels via acute increases in extravascular pressure elicits rapid vasodilatation in humans. In healthy adults, we measured forearm blood flow (Doppler ultrasound) and calculated forearm vascular conductance (FVC) responses to whole forearm compressions and isometric muscle contractions with the arm above heart level. We used several experimental protocols to gain insight into how mechanical factors contribute to contraction-induced rapid vasodilatation. The findings from the present study clearly indicate that acute increases in extravascular pressure (200 mmHg for 2 s) elicit a significant rapid vasodilatation in the human forearm (peak DeltaFVC approximately 155%). Brief, 6 s sustained compressions evoked the greatest vasodilatation (DeltaFVC approximately 260%), whereas the responses to single (2 s) and repeated compressions (five repeated 2 s compressions) were not significantly different (DeltaFVC approximately 155% versus approximately 115%, respectively). This mechanically induced vasodilatation peaks within 1-2 cardiac cycles, and thus is dissociated from the temporal pattern normally observed in response to brief muscle contractions ( approximately 4-7 cardiac cycles). A non-linear relation was found between graded increases in extravascular pressure and both the immediate and peak rapid vasodilatory response, such that the responses increased sharply from 25 to 100 mmHg, with no significant further dilatation until 300 mmHg (maximal DeltaFVC approximately 185%). This was in contrast to the linear intensity-dependent relation observed with muscle contractions. Our collective findings indicate that mechanical influences contribute largely to the immediate vasodilatation (first cardiac cycle) observed in response to a brief, single contraction. However, it is clear that there are additional mechanisms related to muscle activation that continue to cause and sustain vasodilatation for several more cardiac cycles after contraction. Additionally, the potential contribution of mechanical influences to the total contraction-induced hyperaemia appears greatest for low to moderate intensity single muscle contractions, and this contribution becomes less significant for sustained and repeated contractions. Nevertheless, this mechanically induced vasodilatation could serve as a feedforward mechanism to increase muscle blood flow at the onset of exercise, as well as in response to changes in contraction intensity, prior to alterations in local vasodilating substances that influence vascular tone.

Figure 1

Schematic timeline for Protocol 1 Acute increases in extravascular pressure were acheived via whole forearm compression with a custom-made cuff utilizing pressures of 100 and 200 mmHg. Single compressions were performed with cuff inflated for 2 s, sustained compressions were performed with cuff inflated for 6 s, repeated compressions were performed with cuff inflated for 2 s followed by 1 s of deflation for 5 cycles. Each compression trial was preceded and followed by 2 min of rest. Isometric handgrip was performed at ∼20% maximum voluntary contraction in a similar fashion. (See Methods for more detail).

Figure 2

Rapid vasodilatory responses to acute increases in extravascular pressure Significant forearm vasodilatation (P < 0.05) was observed for all compression conditions at 100 and 200 mmHg of cuff pressure (A–C). A brief, 6 s sustained compression at 200 mmHg evoked the largest rapid vasodilatory response when compared with single or repeated compressions (D). *P < 0.05 versus 100 mmHg cuff pressure within specific condition; †P < 0.05 versus single and repeated compressions.

Figure 3

Temporal association between mechanically and contraction-induced rapid vasodilatation Peak vasodilator responses to mechanically induced vasodilatation occurred within 1–2 cardiac cycles, whereas the peak responses to isometric contractions (∼20% maximum voluntary contraction) typically occurred in ∼4 cardiac cycles (A and B). Further, the peak and total vasodilatation for sustained (B) and repeated (C) contractions were significantly greater than the values observed for compressions. In general, mechanically induced vasodilatation was temporally dissociated from vasodilatation observed in response to muscle contractions. *P < 0.05 versus compression; †P < 0.05 versus contraction.

Figure 4

Effects of graded extravascular pressure and contraction intensity on rapid vasodilatation All cuff compressions and muscle contractions elicited rapid vasodilatation (A and D). A non-linear relation was found between forearm cuff pressure and the immediate (first cardiac cycle post; B) and peak rapid vasodilatation (C), whereas the relation was linear with respect to contraction intensity (E and F). Subjects achieved ∼95% maximum voluntary contraction for the ‘∼100%’ trial. *P < 0.05 versus zero; †P < 0.05 versus 25 mmHg; ‡P < 0.05 versus ≤ 50 mmHg; #P < 0.05 versus ≤ 75 mmHg; ##P < 0.05 versus ≤ 200 mmHg.

Figure 5

Relation between estimated intramuscular pressure and rapid vasodilatation for compressions and contractions Based on findings from Sadamoto et al. (1983), we conservatively estimated intramuscular pressure for the various isometric contraction intensities and compared the immediate (first cardiac cycle post) and peak vasodilatation observed in response to contractions and cuff compressions at these pressures. This figure illustrates that mechanically induced vasodilatation contributes largely to the immediate response (A), and that the mechanical contribution to the peak contraction-induced vasodilatation (B) is greatest for low levels of contraction intensity, and becomes progressively less as intensity increases. *P < 0.05 versus compressions at same estimated intramuscular pressure.

Figure 6

Effects of muscle and nerve stimulation on forearm vasodilator responses and the temporal association with mechanically and voluntary contraction-induced rapid vasodilatation Electrical stimulation of both the forearm muscle belly and median nerve evoked a significant vasodilatation (P < 0.05). Of importance, when these responses were compared with those following voluntary contractions, the temporal pattern was similar. By contrast, the temporal pattern of the mechanically induced vasodilatation was dissociated from all muscle contraction conditions (n = 4.) Peak vasodilator responses for both forearm compressions and voluntary contractions were matched to those observed in response to electrical stimulation. Maximum voluntary contraction, 10% for three subjects and 25% for one subject.