Guanethidine sympathectomy of mature rats leads to increases in calcitonin gene-related peptide and vasoactive intestinal polypeptide-containing nerves

Abstract

Changes in the innervation of the heart (right atrium), mesenteric blood vessels, vas deferens and superior cervical ganglia have been examined following long-term sympathectomy of the mature rat. Patterns of innervation were investigated by histochemical and immunohistochemical techniques, while levels of noradrenaline and neuropeptides were measured by neurochemical assays. Large doses of guanethidine (80mg/kg) were given daily for four weeks to 12–14 week-old male rats which were killed at 18–20 weeks of age. Catecholamine-containing nerves were severely depleted or absent in all tissues, together with a reduction in noradrenaline content. Neuropeptide Y levels were depleted by 97% in vas deferens, 78% in mesenteric vein and 50% in right atrium and superior cervical ganglion. Increases in levels of calcitonin gene-related peptide were seen in the mesenteric vein (up seven-fold), superior cervical ganglia (up 11-fold) and vas deferens (prostatic portion up three-fold), which were also evident by assessment of immunolabelling of nerve fibres. Calcitonin gene-related peptide levels were not increased in the right atrium. In addition, an increase in vasoactive intestinal polypeptide-immunoreactive nerve fibre density was seen in the mesenteric artery and vas deferens, although no significant differences were observed in assays of vasoactive intestinal peptide levels in any tissue. No changes were seen in the innervation of any of the tissues by substance P-immunoreactive nerve fibres either by immunohistochemical or immunochemical assay assessment. This study indicates that there are selective changes in the mature nervous system in response to the loss of sympathetic nerves. Differences between these changes and the response of the developing nervous system to long-term sympathectomy are discussed.