Non-noradrenergic sympathetic neurons project to extramuscular feed arteries and proximal intramuscular arteries of skeletal muscles in guinea-pig hindlimbs

This study set out to examine the non-noradrenergic sympathetic innervation of extramuscular and intramuscular arterial vessels supplying hindlimb muscles of guinea-pigs, using multiple-labelling fluorescence immunohistochemistry. Non-noradrenergic axons, identified by their immunoreactivity (IR) to vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), innervated nearly all (≤ 88%) extramuscular feed arteries supplying muscles of the medial thigh. The distribution of non-noradrenergic axons along extramuscular feed arteries was often patchy, with increased density near some branch points. The density of axons with VIP-IR and NPY-IR at the adventitia-medial junction of the larger extramuscular arteries was similar to the density of noradrenergic axons identified by IR to tyrosine hydroxylase (TH) and NPY. The proportion of arterial vessels innervated by VIP-IR axons decreased in more distal, intramuscular arterial segments, and when present, the VIP-IR axons were fewer in number than TH-IR axons innervating the same segments. Distal arterioles (< 20 μm diameter) were never innervated by VIP-IR axons, but always by TH-IR axons. The non-noradrenergic sympathetic neurons are almost certainly vasodilator neurons. The prominent innervation of extramuscular feed arteries by sympathetic non-noradrenergic neurons has not been reported previously, even in cats and dogs where there is good physiological evidence for a sympathetic vasodilator response in skeletal muscles. The present morphological results provide compelling reasons for re-evaluating the functional role of sympathetic vasodilation in skeletal muscles of rodents, particularly in relation to the role of feed arteries in neural regulation of muscle blood flow.