This presentation will supplement earlier Paton lectures concerning central nervous organisation of cardiovascular control by concentrating on subcortical & peripheral pathways which subserve circulatory homeostasis.Baroreflex control of long term blood pressure – It had earlier been proposed (by AC Guyton & others) that arterial baroreflex mechanisms were mainly involved in short term beat to beat blood pressure (BP) control, but not longer-term levels of pressure. This view arose from BP recordings made in isolated conscious dogs that had earlier undergone carotid & cardiac denervation. Their BP was raised by only a few mmHg, which was interpreted then as relatively insignificant. At that time it was not known that the arterial baroreflexes had effects on sodium & water elimination via renal nerves, as well as the more easily demonstrated effects on heart rate, cardiac contractility, & peripheral vascular tone. 40 years or so later T. Thrasher showed that baroreceptor unloading caused nervously mediated renal sodium retention & thus longer term BP elevation.Interventions to control blood pressure – Earlier attempts to lower malignant hypertension in man by splanchnic denervation (Smithwick) were successful but accompanied by severe postural hypotension. Another surgical approach was to stimulate the carotid sinus nerves (CSN) by an implantable device. Although this was initially successful longer-term results were marred by damage to the nerve or its blood supply.New methods of CSN stimulation in man are now successful long term, by avoidance of dissection of the CSN using stimulation of the receptors by electrodes applied to the adventitia of the sinus. The implanted generator is now similar in size to a cardiac pacemaker.Non-drug therapy for hypertension has recently used renal denervation by electrical damage applied by a catheter introduced percutaneously from the groin into each renal artery. Earlier trials (Esler & colleagues in Melbourne) showed impressive long lasting BP reduction in patients with drug resistant hypertension. Since this technique did not involve surgery or device implantation it rapidly became the treatment of choice, compared with baroreceptor stimulation, & is now in clinical use. However the US FDA required a properly blinded controlled randomised trial before implementation in the US. In January 2014 it was announced that this trial (Symplicity-3) was negative! So far no further details are available. Preliminary results will be given at the meeting of the American College of Cardiology at the end of March 2014.Methods to assess autonomic tone in man – I will now discuss the use of methods to assess autonomic tone in man. Historically these have evolved from measurements of BP or pulse rate to obtain a measure of arousal, or urine/blood catecholamines, which of course are very indirect assessments (which do not take account of turnover or of tissue sensitivity). Ambulatory BP (ABP) or home BP measures go some way to avoid the arousal caused by medical/nurse observers, but have other problems. Another more direct method is to measure sweating & skin conductivity. All these techniques are imperfect & none (except heart rate) gives any measure of parasympathetic tone. For this reason there has been considerable interest in Power Spectral Analysis (PSA) of heart rate & BP variability which can give an indirect measure of sympatho-vagal balance. It is not possible to completely validate this method, but responses to actions such as postural change from lying to standing, or changes in arousal from sleep to wakefulness, alter PSA measures which demonstrate parallel changes in sympathetic or in vagal tone.Music therapy – The use of music is not only specific to man, but dates back thousands of years. The appreciation of music is confined to man, despite the so called Mozart effect of music on milk yield in cows. The published data on the latter is sparse & poorly controlled.Music can entrain inherent autonomic rhythms in man. Specifically it can entrain the 10 sec Mayer waves in BP & can increase measures of vagal tone. But claims that music therapy can be tailored to individual people are poorly controlled. In experiments on young medical students we found that autonomic responses to 6 differing styles of music (presented in random order) were the same – whatever the individual’s pre-stated musical preference. However the differing responses of the students who were musically trained were greater than the responses of the others.Conclusion – Hypertension treatments have multiplied over the last 40-50 years. But many patients fail to continue treatment long-term, due to side effects or cost. There are now practical physiological alternatives to drug treatment of human hypertension.