Sympathetic nerves inhibit conducted vasodilatation along feed arteries during passive stretch of hamster skeletal muscle

Abstract

Ascending vasodilatation is integral to blood flow control in exercising skeletal muscle and is attributable to conduction from intramuscular arterioles into proximal feed arteries. Passive stretch of skeletal muscle can impair muscle blood flow but the mechanism is not well understood. We hypothesized that the conduction of vasodilatation along feed arteries can be modulated by changes in muscle length. In anaesthetized hamsters, acetylcholine (ACh) microiontophoresis triggered conducted vasodilatation along feed arteries (diameter, 50-70 microm) of the retractor muscle secured at 100 % resting length or stretched by 30 %. At 100 % length, ACh evoked local dilatation (> 30 microm) and this response conducted rapidly along the feed artery (14 +/- 1 microm dilatation at 1600 microm upstream). During muscle stretch, feed arteries constricted approximately 10 microm (P < 0.05) and local vasodilatation to ACh was maintained while conducted vasodilatation was reduced by half (P < 0.01). Resting diameter and conduction recovered upon restoring 100 % length. Sympathetic nerve stimulation (4-8 Hz) produced vasoconstriction and attenuated conduction in the manner observed during muscle stretch, as did noradrenaline or phenylephrine (10 nM). Inhibiting nitric oxide production (Nomega-nitro-L-arginine, 50 microM) produced similar vasoconstriction yet had no effect on conduction. Phentolamine, prazosin, or tetrodotoxin (1 microM) during muscle stretch abolished vasoconstriction and restored conduction. Inactivation of sensory nerves with capsaicin had no effect on vasomotor responses. Thus, muscle stretch can attenuate conducted vasodilatation by activating alpha-adrenoreceptors on feed arteries through noradrenaline released from perivascular sympathetic nerves. This autonomic feedback mechanism can restrict muscle blood flow during passive stretch.

Figure 1. Experimental protocol for muscle stretch and conduction

A, schematic diagram illustrating hamster retractor muscle with feed artery giving rise to arteriolar networks (not to scale). B, representative records of conducted vasodilatation observed at 400 μm (site 1) and at 1600 μm (site 2) upstream from ACh stimulus (1 μA, 1 s delivered at time 0). During muscle stretch, diameter change was maintained at site 1 and attenuated by half at site 2. Values of 100 % and 130 % refer to muscle length (L_O) as described in Methods. Note vasoconstriction during muscle stretch.

Figure 2. Muscle stretch attenuates conducted vasodilatation

A and B indicate the absolute change in diameter along feed artery at sites upstream from ACh stimulus. A represents experiments based upon in situ resting length, L_IS (n = 16). The slope of the line describing the decay in the amplitude of conducted vasodilatation between 400 and 1600 μm along feed arteries (expressed as: μm diameter change (μm vessel length)⁻¹) increased from −0.0054 ± 0.0024 at 100 % of L_IS to −0.0115 ± 0.0024 at 130 % of L_IS. B represents experiments based upon optimal length for tension production, L_O (n = 17). The slope of the line (defined as in A) describing conducted vasodilatation increased from −0.0053 ± 0.0017 at 100 % L_O to −0.0086 ± 0.0012 at 130 % L_O. C and D illustrate the data in A and B, respectively, with values at each conducted site normalized to the change in diameter at the 400 μm site. Vessel diameters are in Table 1. * Significant difference from response at 130 % (P < 0.05).

Figure 3. Perivascular nerve stimulation (PNS) and adrenoreceptor agonists attenuate conducted vasodilatation

Conducted vasodilatation was attenuated during PNS with muscles held at 100 % of L_IS (A, n = 4) or at 100 % of L_O (B, n = 3). Stretching muscles to 130 % of respective reference lengths attenuated conduction in the manner recorded during PNS. At 100 % of L_IS, noradrenaline (NA, 10 nm) attenuated conducted vasodilatation (C, n = 5). At 100 % of L_O, phenylephrine (PE, 10 nm) attenuated conducted vasodilatation (D, n = 10). Data are normalized as in Fig. 2. Vessel diameters are in Table 1. * Significant difference from responses at 100 % during PNS or with noradrenaline or phenylephrine (P < 0.05). + Significant difference from responses at 130 % (P < 0.05).

Figure 4. Attenuation of conducted vasodilatation during muscle stretch is inhibited by blockade of α-adrenoreceptors

During muscle stretch, addition of phentolamine (1 μm for L_IS (A, C);10 μm for L_O (B, D)) blocked the attenuation of conducted vasodilatation whether 100 % L_IS (A, n = 5) or L_O (B, n = 6) was used for initial reference length. Phentolamine also prevented the attenuation of conducted responses induced by noradrenaline (C, n = 5) or phenylephrine (D, n = 4). Data are normalized as in Fig. 2. Vessel diameters are given in Table 1. * Significant difference from response at 130 % (P < 0.05).

Figure 5. Vasoconstriction with L-NA does not attenuate conducted vasodilatation

With muscles at 100 % of L_IS (A, n = 4) or of L_O (B, n = 4), vasoconstriction with L-NA to the same extent as that observed with 130 % muscle stretch had no effect on conducted vasodilatation. Data are normalized as in Fig. 2. Vessel diameters are given in Table 1. * Significant difference from responses at 130 % (P < 0.05).