Aberdeen, Judith Anne; (1991) Perivascular nerves: Changes in ageing and disease. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis presents a study of the changes in perivascular catecholamine(CA)- and peptide-containing nerves of peripheral and central blood vessels during ageing, after sympathectomy, in diabetes and atherosclerosis and after acrylamide poisoning. Histochemical changes in innervation on blood vessels during ageing was studied in rats and rabbits and assessed qualitatively and quantitatively using image analysis. The density of CA-containing and neuropeptide Y-immunoreactive (NPY-IR) nerve fibres did not change in either species over the ages studied. In rabbits, fine, varicose, calcitonin gene-related peptide (CGRP)-IR nerve fibres decreased with age while vasoactive intestinal polypeptide (VIP)- and substance P (SP)-IR nerve fibres showed increased with age. In rats, the density of VIP-IR nerve fibres could not be seen to change however, CGRP- and SP-IR nerve fibres increased steadily with age. Quantitative measurements revealed that both CGRP- and SP-IR nerve fibres increase similarly until 12 months of age then SP-IR nerve fibres begin to decrease while CGRP-IR nerve fibres continue to increase in number. Vascular innervation patterns were also studied in two other species. The sheep middle cerebral artery was shown to have dense plexuses of VIP-IR, CGRP-IR and CA-containing nerves. CA-containing, NPY-, CGRP-, VIP- and SP-IR perivascular nerves were revealed in the guinea pig spiral modialor artery of the inner ear; CGRP- and SP-IR were colocalized. Sympathectomy by chronic treatment of young and mature rats with guanethidine led to large increases in CGRP-IR nerves in blood vessels while CA and NPY-IR nerves were virtually abolished. SP-IR nerves were unchanged. VIP-IR nerves were unchanged when young rats were treated with guanethidine, but showed in increase when adults were treated. Sympathectomy by treatment of neonatal rats with antibodies to nerve growth factor (NGF) produced decreases in CGRP- and SP-IR nerves as well as CA-containing and NPY-IR nerves, but VIP-IR nerve fibres were unchanged. Since by 8 weeks of age NPY-IR but not CA-containing nerves were found to reinnervate the mesenteric artery, the likelihood that NPY-containing non-sympathetic nerves are involved is proposed. The neuropathies caused by diabetes and acrylamide poisoning in rats and by atherosclerosis in rabbits have been studied. In both diabetes and acrylamide poisoning CA-containing, NPY-, CGRP- and SP-IR nerves were decreased and the nerves often showed structural damage. However, VIP-IR nerves increased slightly in diabetic vessels, but decreased after acrylamide poisoning. Atherosclerotic vessels showed little change in perivascular innervation patterns except for a slight decrease in SP- and CGRP-IR nerve densities.

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