Content and delivery preferences for information to support the management of high blood pressure.

Blood pressure(BP) management interventions have been shown to be more effective when accompanied by appropriate patient education. As high BP remains poorly controlled, there may be gaps in patient knowledge and education. Therefore, this study aimed to identify specific content and delivery preferences for information to support BP management among Australian adults from the general public. Given that BP management is predominantly undertaken by general practitioners(GPs), information preferences to support BP management were also ascertained from a small sample of Australian GPs. An online survey of adults was conducted to identify areas of concern for BP management to inform content preferences and preferred format for information delivery. A separate online survey was also delivered to GPs to determine preferred information sources to support BP management. Participants were recruited via social media. General public participants (n = 465) were mostly female (68%), >60 years (57%) and 49% were taking BP-lowering medications. The management of BP without medications, and role of lifestyle in BP management were of concern among 30% and 26% of adults respectively. Most adults (73%) preferred to access BP management information from their GP. 57% of GPs (total n = 23) preferred information for supporting BP management to be delivered via one-page summaries. This study identified that Australian adults would prefer more information about the management of BP without medications and via lifestyle delivered by their GP. This could be achieved by providing GPs with one-page summaries on relevant topics to support patient education and ultimately improve BP management.

Exploration of diet, physical activity, health knowledge and the cardiometabolic profile of young adults with intellectual disability.

BACKGROUND: Young adults with intellectual disability (ID) are experiencing early mortality, and it is suggested that they are living with undiagnosed cardiovascular and metabolic risk factors (hereafter referred to as cardiometabolic). METHODS: We investigated the association between modifiable risk factors and cardiometabolic health profile in adults with ID aged 18-45 years through clinical evaluation of traditional cardiometabolic parameters, and assessment of physical activity levels, diet and associated health knowledge. RESULTS: We found that young adults with ID have an increased obesity (mean body mass index; ID group: 32.9 ± 8.6 vs. control group: 26.2 ± 5.5, P = 0.001), are engaging in less physical activity than the age-matched general population (total activity minutes per week; ID group: 172.2 ± 148.9 vs. control group: 416.4 ± 277.1, P < 0.001), and overall have unhealthier diets. Additionally, knowledge about nutrition and physical activity appears to be an important predictor of cardiometabolic risk in this population. If young people with ID are to improve their cardiometabolic health to reduce morbidity and early mortality, we need to further explore how to consistently apply health messaging to get lasting behavioural change in this population.

Pain duration is associated with increased muscle sympathetic nerve activity in patients with Achilles tendinopathy.

Tendinopathy is a common condition, which has been linked to surrogate measures of sympathetic nervous system (SNS) activity and insulin resistance. This study aimed to compare in vivo measures of the SNS and insulin resistance between individuals with and without Achilles tendinopathy. This case-control study compared Achilles tendinopathy sufferers to healthy controls. SNS activity was quantified using muscle sympathetic nerve activity (MSNA), while metabolic status was assessed via a modified glucose tolerance test and fasting lipid panel. Ultrasound tissue characterization assessed tendon structure. Resting MSNA did not differ between the 15 cases and 20 controls. Tendon pain duration in tendinopathy patients was correlated with burst frequency (R2 =.32, P=.02) and burst incidence (R2 =.41, P=.01) of MSNA. After adjusting for multiple comparisons, there was a trend suggesting fasting glucose was greater in cases (median 4.80, IQR .70 in cases vs 4.51, .38 in controls) and correlated with pain severity (R2 =.14, P=.03), but no other metabolic measures were associated with tendon pain/structure. This study indicates that SNS activity is associated with tendon pain duration, building on previous data indicating the SNS is involved in recalcitrant tendinopathy. Metabolic parameters had little relationship with Achilles tendinopathy in this metabolically homogenous sample. Prospective studies are required to uncover the precise relationship between SNS activity, insulin resistance, and tendinopathy.

A polymorphism in the norepinephrine transporter gene is associated with affective and cardiovascular disease through a microRNA mechanism.

Norepinephrine released from sympathetic nerves is removed from the neuroeffector junction via the action of the norepinephrine transporter (NET). NET impairment is evident in several clinically important conditions including major depressive disorder (MDD), panic disorder (PD), essential hypertension and the postural orthostatic tachycardia syndrome (POTS). We aimed to determine whether a single nucleotide polymorphism (SNP) in the 3' untranslated region (UTR) of the NET gene is associated with NET impairment and to elucidate the mechanisms involved. The analyses were carried out in two cohorts of European ancestry, which included healthy controls and MDD, PD, hypertensive and POTS patients. Compared with controls, cases had significantly higher prevalence of the T allele of rs7194256 (C/T), arterial norepinephrine, depression and anxiety scores, larger left ventricular mass index, higher systolic and diastolic blood pressures, and heart rate. Bioinformatic analysis identified that the microRNA miR-19a-3p could bind preferentially to the sequence created by the presence of the T allele. This was supported by results of luciferase assays. Compared with controls, cases had significantly lower circulating miR-19a-3p, which was associated with pathways related to blood pressure and regulation of neurotransmission. In vitro norepinephrine downregulated miR-19a-3p. In conclusion, the T allele of the rs7194256 SNP in the 3'UTR of the NET gene is more prevalent in diseases where NET impairment is evident. This might be explained by the creation of a binding site for the microRNA miR-19a-3p. A defect in NET function may potentiate the sympathetic neurochemical signal, predisposing individuals with affective diseases to increased risk of cardiovascular disease development.

Soluble vascular endothelial growth factor receptor-1 is reduced in patients with resistant hypertension after renal denervation.

Renal denervation (RDN) has been shown in several studies to reduce blood pressure (BP) in patients with resistant hypertension (RH). Data on potential biomarkers associated with BP changes remain scarce. We evaluated whether soluble vascular endothelial growth factor receptor (sVEGFR-1) is affected by the procedure. A total of 57 patients with RH participated in this study. BP and heart rate were recorded at baseline and at 3 months follow-up, at which time blood samples were collected to determine the levels of sVEGFR-1, VEGF-A, VEGF-C, nitric oxide (NO), soluble vascular adhesion molecule 1 and soluble intracellular adhesion molecule 1. None of the biomarkers had a predictive value that could identify responders vs non-responders to RDN. However, sVEGFR-1 concentration was dramatically reduced after RDN (5913±385 vs 280±57 pg ml-1, P<0.001). At the same time VEGF-A levels were significantly increased (10.0±3.0 vs 55.5±7.9 pg ml-1, P<0.001), without significant changes in VEGF-C. NO levels were significantly increased after RDN in the whole group (82.6±6.2 vs 106.9±7.8 µM, P=0.021). Interestingly, the elevation in NO levels at 3 months was only seen in patients who demonstrated a reduction in systolic BP of ⩾10 mm Hg (78.9±8.3 vs 111.6±11.7 µM, P=0.018). We report a significant reduction in sVEGFR-1 levels after RDN procedure, which was accompanied by a significant increase in VEGF-A concentration as well as NO. Changes in plasma cytokines were not quantitatively linked to magnitude of BP reduction. An RDN-induced reduction in sVEGFR-1 plasma levels and increase in VEGF-A would raise the VEGF-A/sVEGFR-1 ratio, thereby increasing VEGF-A bioavailability to act on its full-length receptor and may contribute to the BP-lowering effect potentially via NO-mediated pathways.

Norepinephrine transporter expression is inversely associated with glycaemic indices: a pilot study in metabolically diverse persons with overweight and obesity.

OBJECTIVE: The objective of this study was to examine the cross-sectional relationship between the expression of norepinephrine transporter (NET), the protein responsible for neuronal uptake-1, and indices of glycaemia and hyperinsulinaemia, in overweight and obese individuals. METHODS: Thirteen non-medicated, non-smoking subjects, aged 58 ± 1 years (mean ± standard error of the mean), body mass index (BMI) 31.4 ± 1.0 kg m-2, with wide-ranging plasma glucose and haemoglobin A1c (HbA1c, range 5.1% to 6.5%) participated. They underwent forearm vein biopsy to access sympathetic nerves for the quantification of NET by Western blot, oral glucose tolerance test (OGTT), euglycaemic hyperinsulinaemic clamp, echocardiography and assessments of whole-body norepinephrine kinetics and muscle sympathetic nerve activity. RESULTS: Norepinephrine transporter expression was inversely associated with fasting plasma glucose (r = -0.62, P = 0.02), glucose area under the curve during OGTT (AUC0-120, r = -0.65, P = 0.02) and HbA1c (r = -0.67, P = 0.01), and positively associated with steady-state glucose utilization during euglycaemic clamp (r = 0.58, P = 0.04). Moreover, NET expression was inversely related to left ventricular posterior wall dimensions (r = -0.64, P = 0.02) and heart rate (r = -0.55, P = 0.05). Indices of hyperinsulinaemia were not associated with NET expression. In stepwise linear regression analysis adjusted for age, body mass index and blood pressure, HbA1c was an independent inverse predictor of NET expression, explaining 45% of its variance. CONCLUSIONS: Hyperglycaemia is associated with reduced peripheral NET expression. Further studies are required to identify the direction of causality.

Neuroendocrine adaptations to bariatric surgery.

The global epidemic of obesity and its related disease in combination with robust physiological defence of intentional weight loss generates a pressing need for effective weight loss therapies. Bariatric surgery, which works very effectively at delivering substantial sustained weight loss, has been an enigma with respect to mechanism of action. Naive concepts of restriction and malabsorption do not explain the efficacy of the most commonly used bariatric procedures. This century has seen increased interest in unravelling the mystery of the mechanisms underlying surgery associated weight loss with a focus on integrative gastrointestinal (GI) physiology, gut-brain signalling, and beyond weight loss effects on metabolism. GI interventions, some very minor, can alter GI wall stretch and pressure receptors; a range of GI hormones affecting hunger and satiety; bile acid metabolism and signalling; the characteristics of GI microbiome; portal vein nutrient sensing; and circulating concentrations of amino acids. Understanding the mechanisms involved should present targets for less invasive effective therapies.

Fat-free mass loss generated with weight loss in overweight and obese adults: What may we expect?

There is concern that intentional weight loss may generate excessive loss of fat-free mass (FFM). Idealists target minimal loss of FFM, while others consider that FFM loss of up to 25% of weight loss is acceptable. In a cross-sectional study of 275 weight-stable, overweight or obese adults, we used whole-body dual-energy X-ray absorptiometry to measure FFM. A range of models was used to estimate the expected ΔFFM/Δweight ratio required to attain the body composition of a weight-stable individual at a lower body mass index (BMI). Higher BMI was associated linearly with higher FFM in men and women. Proportional ΔFFM/Δweight was influenced by sex, BMI and age. Direct scatter plot analysis, quadratic curve fit modelling and linear FFM-BMI modelling provided similar estimates for each model of ΔFFM/Δweight ratio, with 40% for men and 33% for women. These results show that the 25% rule is inappropriate and our estimates are higher than those generally reported after intentional weight loss indicating favourable preservation of FFM.

'Obesity paradox' misunderstands the biology of optimal weight throughout the life cycle.

The 'obesity paradox' refers to observations that run counter to the thesis that normal weight (BMI 18.5-24.9 g/m(2)) provides the lowest mortality and higher weight is associated with greater mortality. We argue that the weight of lowest mortality is influenced by aging and chronic disease, with mortality advantage extending into the overweight and even class I obese ranges under some circumstances. A focus on quality nutrition, physical activity, fitness, and maintaining function in these weight ranges may be preferable to a focus on intentional weight loss, which has uncertain effects. The 'obesity paradox' is no 'paradox' if one defines and interprets 'ideal' weight appropriately.

Role of the sympathetic nervous activity in hypertension-update in 2014.

Many reviews focused on the role of sympathetic nervous activity in hypertension have been published. Recently a new treatment, radiofrequency renal denervation for the treatment of resistant hypertension has been developed and examined in several clinical trials such as the Symplicity HTN and EnligHTN studies. In the Symplicity HTN-1 study the efficacy for lowering blood pressure remained satisfactory at 3 years follow up and many ancillary ameliorative effects have been reported including cardiovascular, psychosocial, and metabolic effects. The purpose of this review is to provide the current findings on the relationships between sympathetic nerve activity and hypertension, especially focus on the importance of renal sympathetic nervous activity for the onset and development of hypertension. In addition, the methods to assess sympathetic nervous activity are reviewed.

The renal denervastion was developed for the treatment-resistant hypertensive patients, and excessive confidence of the efficacy and safety existed by the end of 2013, although several issues on the efficacy and safety were reported in 2014. Furthermore, long-term efficacy and impact on renal function have been unclear. Those issues have to be clear for clinical usage. This review will also address the recent data from the renal denervation.

Chronic distress and acute vascular stress responses associated with ambulatory blood pressure in low-testosterone African men: the SABPA Study.

It is known that low testosterone (T) and high cortisol levels are associated with hypertension as well as with chronic stress, linking stress with elevated blood pressure (BP). However, the association between acute stress-, chronic stress responses and BP is not clear in Africans. Therefore, we examined the association between cortisol, psychological distress and BP responses in low- and high-T male subgroups. Beat-to-beat and ambulatory blood pressure (ABPM) and electrocardiogram measures were obtained. Serum samples were collected and analyzed for sex hormones and cortisol. Chronic psychological distress was verified with the General Health Questionnaire and acute stress with the cold pressor test. More chronic psychological distress was observed in both low- and high-T Africans compared with the Caucasians. The low-T Africans tended to have more ischemic events (P=0.06) and ABPM values (P⩽0.01) than any of the other groups. Both chronic distress (cortisol) and acute stress (total peripheral resistance cold pressor responses) were associated with ABPM in the low-T African group. Acute and chronic stress may contribute to increased BP in low-T African men. Their cortisol and vascular responses supported a tendency for ischemia, increasing their risk for coronary artery disease.

Ephedrine activates brown adipose tissue in lean but not obese humans.

AIMS/HYPOTHESIS: Brown adipose tissue (BAT) activation increases energy consumption and may help in the treatment of obesity. Cold exposure is the main physiological stimulus for BAT thermogenesis and the sympathetic nervous system, which innervates BAT, is essential in this process. However, cold-induced BAT activation is impaired in obese humans. To explore the therapeutic potential of BAT, it is essential to determine whether pharmacological agents can activate BAT. METHODS: We aimed to determine whether BAT can be activated in lean and obese humans after acute administration of an orally bioavailable sympathomimetic. In a randomised, double-blinded, crossover trial, we administered 2.5 mg/kg of oral ephedrine to nine lean (BMI 22 ± 1 kg/m²) and nine obese (BMI 36 ± 1 kg/m²) young men. On a separate day, a placebo was administered to the same participants. BAT activity was assessed by measuring glucose uptake with [¹8F]fluorodeoxyglucose and positron emission tomography-computed tomography imaging. RESULTS: BAT activity was increased by ephedrine compared with placebo in the lean, but unchanged in the obese, participants. The change in BAT activity after ephedrine compared with placebo was negatively correlated with various indices of body fatness. CONCLUSIONS/INTERPRETATION: BAT can be activated via acute, oral administration of the sympathomimetic ephedrine in lean, but not in obese humans.

Defensive active coping facilitates chronic hyperglycaemia and endothelial dysfunction in African men: the SABPA study.

BACKGROUND: Dissociation between behavioural defensive active coping (AC) control albeit physiological "loss of control" responses was associated with silent ischaemia and structural wall abnormalities in African men. Whether it applies to structural alterations and endothelial dysfunction is uncertain. We therefore aimed to determine AC ethnic-gender specific receiver operating characteristic (ROC) carotid intima media far wall (CIMTf) cut points best associated with 24-h BP, -silent ischaemia and glycated haemoglobin (HbA1c). METHODS: Participants included African and Caucasians (N=317) without pre-existing stroke or atrial fibrillation, aged 45 ± 9 years. The Coping Strategy Indicator was used to measure AC. Ultrasound CIMTf, ambulatory BP, silent ischaemia and fasting blood samples were obtained. RESULTS: Between 69 and 77% of AC African men showed above normal diastolic BP and HbA1c levels compared to 44-48% of AC Caucasian men. In AC African women, 41-60% showed above normal BP, silent ischaemia and HbA1c levels compared to 17-44% of their Caucasian counterparts. ROC curve analyses, detecting optimal CIMTf cut points, ranged between 0.57 and 0.65 mm (BP) and 0.71 and 0.74 mm (silent ischaemia) in AC ethnic-gender groups. Only HbA1C (>5.7%), with a sensitivity/specificity 47%/74%, after controlling for confounders, predicted structural alterations at an optimal cut point of 0.69 mm in AC African men (OR 4.5; 95% CI 2.93-18.73). CONCLUSION: Novel findings of behavioural resilience were apparent in the AC African female despite a high prevalence of risk markers. In AC males, chronic hyperglycaemia facilitated endothelial dysfunction, i.e. a physiological "loss of control" and susceptibility to stroke risk.

The effects of dietary weight loss with or without exercise training on liver enzymes in obese metabolic syndrome subjects.

AIM: Insulin resistance and visceral adiposity are predisposing factors for fatty liver disease. The main objectives of this study were (i) to compare the effects of caloric restriction (CR) alone or together with moderate-intensity aerobic exercise training (CR+EX) on liver enzymes, a surrogate marker of liver injury, in obese metabolic syndrome (MetS) subjects and (ii) to identify anthropometric, metabolic, cardiovascular and dietary predictors of changes in liver enzymes. METHODS: Sedentary men and women (n = 63), aged 55 ± 6 (s.d.) years with body mass index 32.7 ± 4.1 kg/m(2) and confirmed MetS, were randomized to 12-week CR, CR+EX or no treatment (Control). RESULTS: Weight loss averaged 7.6% in the CR and 9.1% in the CR+EX group (time effect, p < 0.001; group effect, p = 0.11); insulin sensitivity improved by 49 and 45%, respectively (both p < 0.001). Fitness (maximal oxygen consumption) increased by 19% in the CR+EX group only (p < 0.001). Alanine aminotransferase (ALT) levels decreased by 20% in the CR and 24% in the CR+EX group (time effect, both p < 0.001; group effect, p = 0.68); corresponding values for γ-glutamyltransferase (GGT) were -28 and -33%, respectively (time effect, both p < 0.001; group effect, p = 0.28). Reduction in abdominal fat mass (measured by DXA from L1 to L4) independently predicted ΔALT (r = 0.42, p = 0.005) and ΔGGT (r = 0.55, p < 0.001), whereas change in dietary saturated fat intake was independently associated with ΔALT (r = 0.35, p = 0.03). CONCLUSIONS: Reductions in central adiposity and saturated fat intake are key drivers of improvement in liver enzymes during lifestyle interventions. Exercise training did not confer significant incremental benefits in this study.

Sex differences in postnatal growth and renal development in offspring of rabbit mothers with chronic secondary hypertension.

Previously, we demonstrated that adult blood pressure was increased in offspring of rabbit mothers with chronic secondary renal hypertension. Our study identified sex-specific differences in the programming of hypertension, with female, not male, offspring, having increased blood pressure at 30 wk of age. The aim of this study was to characterize the maternal hypertension during pregnancy to determine potential programming stimuli. Further, we examined the impact of chronic maternal hypertension on offspring birth weight, nephron number, and renal noradrenaline content (as an index of renal innervation density). Three groups of mothers and their offspring were studied: two-kidney, one-wrap (2K-1W, n = 9 mothers) hypertensive, two-kidney, two-wrap (2K-2W, n = 8) hypertensive, and a sham-operated group (n = 9). Mean arterial blood pressure was increased by approximately 20 mmHg throughout pregnancy in both hypertensive groups compared with sham mothers (P(G) < 0.001). Plasma renin activity (PRA; P(G) < 0.05) and aldosterone (P(G) < 0.05) levels were increased during gestation in the 2K-1W, but not the 2K-2W mothers. Birth weight was increased by approximately 20% in offspring of both groups of hypertensive mothers (P(T) < 0.001), though this was associated with a reduction in litter size. Renal noradrenaline content was increased ( approximately 40%, P < 0.05) at 5 wk of age in female 2K-1W offspring compared with sham offspring. Glomerular number was not reduced in female offspring of either group of hypertensive mothers; however, glomerular tuft volume was reduced in female 2K-2W offspring (P < 0.05), indicative of a reduction in glomerular filtration surface area. In conclusion, the two models of renal hypertension produced differential effects on the offspring. The impact of a stimulated maternal renin-angiotensin system in the 2K-1W model of hypertension may influence development of the renal sympathetic nerves and contribute to programming of adult hypertension.

The role of catecholamines in memory impairment in chicks following reduced gas exchange in ovo.

We have shown previously that reducing gas exchange to chick embryos by half wrapping eggs with an impermeable membrane from either days 14-18 (W14-18) or days 10-18 (W10-18) of the 21 day incubation results in post-hatch memory deficits. In the W10-18 chicks, short-term memory following training is impaired, whereas in the W14-18 chicks, memory is intact for 30 min but does not consolidate into long-term storage. The reduction in gas exchange caused by half wrapping eggs resulted in alterations in hematocrit, O2 and CO2 tensions suggesting that the embryos are hypoxic and hypercapnic. Our aim was to test the hypothesis that increases in circulating levels of catecholamines in ovo, as a result of hypoxia, lead to a disturbance of the central noradrenergic pathways resulting in cognitive impairment. Noradrenaline is critical for memory consolidation and a disturbance during development could compromise cognitive ability. In the present study, plasma noradrenaline levels were significantly elevated compared with control levels 2 days after hatch in W14-18 chicks. There was also a decrease in tissue noradrenaline concentration in the anterior forebrain in both W14-18 and W10-18 chicks. The differential ability of centrally administered beta2- and beta3-adrenoceptor agonists to overcome the memory deficit post-training, suggests altered responsiveness of central beta2-adrenoceptors to noradrenaline in W14-18 chicks. By comparing the W10-18 and W14-18 chicks with those from eggs wrapped from W10-14 we show that it is the timing of the prenatal hypoxia, rather than its duration, that determines the nature of cognitive dysfunction. We conclude that prenatal hypoxia induced by restriction of gas exchange can disrupt or alter central noradrenergic transmission causing cognitive impairment.

Seasonal differences in the effect of isolation and restraint stress on the luteinizing hormone response to gonadotropin-releasing hormone in hypothalamopituitary disconnected, gonadectomized rams and ewes.

Stress responses are thought to act within the hypothalamopituitary unit to impair the reproductive system, and the sites of action may differ between sexes. The effect of isolation and restraint stress on pituitary responsiveness to GnRH in sheep was investigated, with emphasis on possible sex differences. Experiments were conducted during the breeding season and the nonbreeding season. In both experiments, 125 ng of GnRH was injected i.v. every 2 h into hypothalamopituitary disconnected, gonadectomized rams and ewes on 3 experimental days, with each day divided into two periods. During the second period on Day 2, isolation and restraint stress was imposed for 5.5 h. Plasma concentrations of LH and cortisol were measured in samples of blood collected from the jugular vein. In the second experiment (nonbreeding season), plasma concentrations of epinephrine, norepinephrine, 3,4-dihydroxyphenylalanine, and 3,4-dihydroxyphenylglycol were also measured. In both experiments, there was no effect of isolation and restraint stress on plasma concentrations of cortisol in either sex. During the breeding season, there was no effect of isolation and restraint stress on plasma concentrations of LH in either sex. During the nonbreeding season, the amplitude of the first LH pulse after the commencement of stress was significantly reduced (P < 0.05) in rams and ewes. In the second experiment, during stress there was a significant increase (P < 0.05) in plasma concentrations of epinephrine in rams and ewes and significantly higher (P < 0.05) basal concentrations of norepinephrine in ewes than in rams. These results suggest that in sheep stress reduces responsiveness of the pituitary gland to exogenous GnRH during the nonbreeding season but not during the breeding season, possibly because of mediators of the stress response other than those of the hypothalamus-pituitary-adrenal gland axis.

Effect of sunlight and season on serotonin turnover in the brain.

Alterations in monoaminergic neurotransmission in the brain are thought to underlie seasonal variations in mood, behaviour, and affective disorders. We took blood samples from internal jugular veins in 101 healthy men, to assess the relation between concentration of serotonin metabolite in these samples and weather conditions and season. We showed that turnover of serotonin by the brain was lowest in winter (p=0.013). Moreover, the rate of production of serotonin by the brain was directly related to the prevailing duration of bright sunlight (r=0.294, p=0.010), and rose rapidly with increased luminosity. Our findings are further evidence for the notion that changes in release of serotonin by the brain underlie mood seasonality and seasonal affective disorder.

Paring down on Descartes: a review of brain noradrenaline and sympathetic nervous function.

1. The conceptual framework of mind-body interaction can be traced back to the seminal observations of the French philosopher and mathematician René Descartes (1596-1650). Descartes succeeded in eliminating the soul's apparent physiological role and established the brain as the body's control centre. 2. While the pivotal role played by the central nervous system (CNS) in the maintenance of physiological and psychological health has long been recognized, the development of methods designed for the direct examination of human CNS processes has only recently come to fruition. 3. There exists a substantial body of evidence derived from clinical and experimental studies indicating that CNS monoaminergic cell groups, in particular those using noradrenaline as their neurotransmitter, participate in the excitatory regulation of the sympathetic nervous system and the development and maintenance of the hypertensive state. 4. In essential hypertension, particularly in younger patients, there occurs an activation of sympathetic nervous outflows to the kidneys, heart and skeletal muscle. The existence of a correlation between subcortical brain noradrenaline turnover and total body noradrenaline spillover to plasma, resting blood pressure and heart rate provides further support for the observation that elevated subcortical noradrenergic activity subserves a sympathoexcitatory role in the regulation of sympathetic preganglionic neurons of the thorocolumbar cord.