The sympathetic nervous system in man in health and disease

Abstract

The work described in this thesis examined the occurrence and consequences of abnormalities of sympathetic nervous function in man in relation to blood pressure control and thermoregulation. The autonomic responses to standing were investigated in elderly subjects with orthostatic hypotension. The sympathetic response to standing was examined by measurement of catecholamines in plasma. No abnormality of cardiac or catecholamine response was found in the elderly subjects with orthostatic hypotension. The noradrenaline response in the subjects with orthostatic hypotension suggested a vascular resistance to endogenous catecholamines. This investigation was extended to a study of the effects of glucose ingestion. Subjects with orthostatic hypotension had normal noradrenaline resposes to glucose but nonetheless they had marked falls of blood pressure which were not observed in control subjects. Both results suggest that elderly subjects with orthostatic hypotension have an abnormality at the level of the adrenoreceptor. Catecholamine responses were also investigated in a patient with Parkinson's disease associated with orthostatic hypotension. This association had previously been described in a number of patients but the physiological basis of the orthostatic hypotension had not been delineated. The findings in this patient showed a failure of catecholamine release in response to standing, probably due to a lesion in the brain stem or spinal cord. Catecholamine responses were also examined in a patient with orthostatic hypotension associated with pernicious anaemia, before and after vitamin B12 replacement therapy. Catecholamine responses were absent before commencement of vitamin therapy. The patient had normal catecholamine responses after commencing vitamin therapy, when orthostatic hypotension no longer occurred. Thus pernicious anaemia may cause orthostatic hypotension due to a failure of noradrenaline release, which is reversed by vitamin B12 replacement therapy. The thermoregulatory and cardiovascular responses to acute heat stress were examined in a group of chronic alcoholics in order to determine the effects of alcoholism on sweating and other thermoregulatory responses. Alcoholics had significantly reduced weight loss and higher temperatures after heat exposure as compared to control subjects. Some alcoholics had impaired distal sweating and there was no evidence of compensatory sweating in unaffected areas. The alcoholic group also had altered cardiovascular responses to heat stress, which might be explained by catecholamine receptor dysfunction. Cardiovascular control in alcoholics was examined further by subjecting alcoholics and controls to lower body negative pressure in order to examine the baroreflex arc. The alcoholics did not have any evidence of reduced baroreflex sensitivity but had altered catecholamine and blood pressure responses which were again in line with a possible adrenoreceptor dysfunction. Study of failure of thermoregulatory function due to neurological disease was extended to a patient with multiple sclerosis who showed absent sweating response to radiant heating but normal vasodilatation. Sweating was induced by pilocarpine electrophoresis, so that the abnormal response was not due to an absence of sweat glands. These findings suggest that vasomotor and sudomotor efferent nerve tracts from the 'thermoregulatory centre' can be discretely isolated and that active sweating is not necessary for heat induced vasodilatation to occur.