Fifty years of research on the physiology and pharmacology of the autonomic nervous system

Abstract

To commemorate the 30th anniversary of Clinical Autonomic Research a journal whose first editorial board I had the honor to be part of I relate some of my professional experiences in autonomic medicine, in particular in physiology and pharmacology. My first serious interaction with the autonomic nervous system was in 1966 when I registered as a candidate for a Doctorate in Medicine (M.D.) degree, in the department of Human Physiology and Pharmacology at the University of Adelaide. Until then, my knowledge of the autonomic nervous system was restricted to what had been covered within my undergraduate medical program and particularly its relationship to the functioning of the cardiovascular system, the alimentary tract, and thermoregulation. The supervisors for my Doctorate degree were Professor Robert (Bob) Whelan and Professor Ivan de la Lande. Whelan was the head of the department with de la Lande as his deputy. They both had a significant interest in the autonomic nervous system. Bob Whelan came from Queen’s University in Belfast (Northern Ireland), where he was a member of a formidable team of cardiovascular physiologists (Roddie, Shepherd, and Whelan) who had published extensively on the control of the peripheral circulation in man. Much of their work involved forearm and hand plethysmography and the study of drugs and exercise on the human circulation. Thus, I was blooded into the art of plethysmography soon after I began my degree. Professor de la Lande, on the other hand, was a biological scientist with a Ph.D. from Melbourne University and his role was to teach me the use of the isolated, perfused central artery of the rabbit ear to study the effects of sympathetic innervation on vascular sensitivity to noradrenaline [1]. We developed a fluorescent histochemical technique to examine catecholamine fluorescence in a variety of human and primate blood vessels, and concluded that the sympathetic nerve endings in the blood vessels are located at the medio-adventitial junction [5, 8, 11]. In addition, we conducted plethysmography studies on the human forearm and demonstrated that both tyramine and ephedrine were indirectly acting sympathomimetics, whose constrictor action on this vascular bed was very dependent on the presence of sympathetic nerves [9, 10]. We further demonstrated the enhancement of the vasoconstrictor action of tyramine, methylamphetamine, and ephedrine by the monoamine oxidase inhibitor tranylcypromine [6]. This finding provided us with a platform to use monoamine oxidase inhibitors, fludrocortisone, and even cheese to increase blood pressure and improve orthostatic symptoms in patients with idiopathic orthostatic hypotension [7, 13]. Because of our interest in autonomic function testing, we received many requests from the Royal Adelaide Hospital, and also from specialists and general practitioners, to evaluate their patients. This led to some interesting reports, among them three cases of orthostatic hypotension with autonomic failure [4]. One of these was a 40-year-old woman with widespread autonomic nervous system degeneration associated with peripheral sensory and motor neuropathy and the Holmes-Adie syndrome. Her autopsy showed widespread amyloid deposition in the sympathetic ganglia, peripheral nerves, heart, and the gastrointestinal system, as the pathological basis for her clinical and physiological findings. We also studied patients with diabetic autonomic neuropathy [2]. I was able to transport my interest in the autonomic nervous system to the department of Rehabilitation Medicine at the College of Physicians and Surgeons of Columbia University in New York, where I was fortunate to work as a Fulbright Scholar in the 1970s. The head of the unit at Columbia (Dr. John Downey) and I had worked closely together in Adelaide and he kindly arranged for a complete set of autonomic testing equipment for me. Also, Dr. Downey’s * Derek Frewin [email protected]