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The mediators of axon terminals innervating the blood vessels and connective tissue compartments of rat peripheral nerves (facial, vagus and sciatic nerve) were investigated by means of double-labeling immunofluorescence. Sympathetic noradrenergic/neuropeptide-Y-immunoreactive axons innervated epi- and endoneurial arterial blood vessels; noradrenergic fibers without neuropeptide Y immunoreactivity terminated in the endoneurium between the axons of the main nerve trunk. Presumably sensory nerve terminals immunoreactive to substance P/calcitonin gene-related peptide supplied epi- but not endoneurial arteries and arterioles, and ran freely in the endoneurial space. Axons immunoreactive to vasoactive intestinal peptide innervated epineurial blood vessels of the facial and vagus nerve but were absent from the vasa nervorum of the sciatic nerve. The findings are in line with the concept, based upon previous pharmacological experiments, of a tonic constrictory and dilatory innervation of vasa nervorum. However, as judged from the distribution patterns of the neurochemically distinct axonal populations, vascular segments of different connective tissue compartments (epi- versus endoneurial) and body regions (sciatic versus cranial nerves) are differentially addressed by each of these axonal populations. This might have implications for the development of region-specific neuropathies.

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