Aims/hypothesis: Previous studies have shown that alterations in vascular, metabolic, inflammatory and haemocoagulative functions characterise the metabolic syndrome. Whether this is also the case for sympathetic function is not clear. We therefore aimed to clarify this issue and to determine whether metabolic or reflex mechanisms might be responsible for the possible adrenergic dysfunction. Methods: In 43 healthy control subjects (age 48.2±1.0 years, mean±SEM) and in 48 untreated agematched subjects with metabolic syndrome (National Cholesterol Education Program's Adult Treatment Panel III Report criteria) we measured, along with anthropometric and metabolic variables, blood pressure (Finapres), heart rate (ECG) and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor manipulation (vasoactive drug infusion technique). Results: Compared with control subjects, subjects with metabolic syndrome had higher BMI, waist circumference, blood pressure, cholesterol, triglycerides, insulin and homeostasis model assessment (HOMA) index values but lower HDL cholesterol values. Sympathetic nerve traffic was significantly greater in subjects with metabolic syndrome than in control subjects (61.1± 2.6 vs 43.8±2.8 bursts/100 heartbeats, p<0.01), the presence of sympathetic activation also being detectable when the metabolic syndrome did not include hypertension as a component. Muscle sympathetic nerve traffic correlated directly and significantly with waist circumference (r= 0.46, p<0.001) and HOMA index (r=0.49, p<0.001) and was inversely related to baroreflex sensitivity (r=−0.44, p<0.001), which was impaired in the metabolic syndrome. Conclusions/interpretation: These data provide evidence that the metabolic syndrome is characterised by sympathetic activation and that this abnormality (1) is also detectable when blood pressure is normal and (2) depends on insulin resistance as well as on reflex alterations.

These data suggest that CO is characterized by a sympathetic activation greater for magnitude than that detectable in PO. This appears not to be related to gender or to baroreflex mechanisms but rather to metabolic factors, i.e. to the greater insulin resistance characterizing CO.

Abstract-Previous studies have shown that essential hypertension and obesity are both characterized by sympathetic activation coupled with a baroreflex impairment. The present study was aimed at determining the effects of the concomitant presence of the 2 above-mentioned conditions on sympathetic activity as well as on baroreflex cardiovascular control. In 14 normotensive lean subjects (aged 33.5Ϯ2.2 years, body mass index 22.8Ϯ0.7 kg/m 2[meanϮSEM]), 16 normotensive obese subjects (body mass index 37.2Ϯ1.3 kg/m 2 ), 13 lean hypertensive subjects (body mass index 24.0Ϯ0.8 kg/m 2 ), and 16 obese hypertensive subjects (body mass index 37.5Ϯ1.3 kg/m 2 ), all age-matched, we measured beat-to-beat arterial blood pressure (by Finapres device), heart rate (HR, by ECG), and postganglionic muscle sympathetic nerve activity (MSNA, by microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Blood pressure values were higher in lean hypertensive and obese hypertensive subjects than in normotensive lean and obese subjects. MSNA was significantly (PϽ0.01) greater in obese normotensive subjects (49.1Ϯ3.0 bursts per 100 heart beats) and in lean hypertensive subjects (44.5Ϯ3.3 bursts per 100 heart beats) than in lean normotensive control subjects (32.2Ϯ2.5 bursts per 100 heart beats); a further increase was detectable in individuals with the concomitant presence of obesity and hypertension (62.1Ϯ3.4 bursts per 100 heart beats). Furthermore, whereas in lean hypertensive subjects, only baroreflex control of HR was impaired, in obese normotensive subjects, both HR and MSNA baroreflex changes were attenuated, with a further attenuation being observed in obese hypertensive patients. Thus, the association between obesity and hypertension triggers a sympathetic activation and an impairment in baroreflex cardiovascular control that are greater in magnitude than those found in either of the above-mentioned abnormal conditions alone. (Hypertension. 2000;36:538-542.) Key Words: nervous system, sympathetic Ⅲ nervous system, autonomic Ⅲ baroreceptors Ⅲ hypertension, essential Ⅲ obesity S tudies on the sympathoadrenal function in animal and human obesity have provided somewhat heterogeneous results. [1][2][3][4][5] However, several recent data have shown that sympathetic activity, as directly assessed by regional norepinephrine (NE) spillover or by microneurographic recording of muscle sympathetic nerve activity (MSNA), is increased in normotensive overweight subjects. 6 -9 A similar increase has been shown to occur in lean individuals with essential hypertension. 10 -14 However, whether this increase and the one characterizing obesity are additive in an obese hypertensive individual is not clear. In one study, the renal spillover of NE was shown to be greater in obese hypertensive than in obese normotensive subjects. 15 However, this was not the case in the cardiac and systemic circulation and in obese and lean hypertensive indivi...

Abstract-Direct and indirect indices of neuroadrenergic function have shown that end-stage renal disease is characterized by a marked sympathetic overdrive. It is unknown, however, whether this phenomenon represents a peculiar feature of end-stage renal disease or whether it is also detectable in the early clinical phases of the disease. The study has been performed in 73 hypertensive patients, of which there were 42 (age: 60.7Ϯ1.8 years, meanϮSEM) with a stable moderate chronic renal failure (mean estimated glomerular filtration rate: 40.7 mL/min per 1.73 m 2 , MDRD formula) and 31 age-matched controls with a preserved renal function. Measurements included anthropometric variables, sphygmomanometric and beat-to-beat blood pressure, heart rate (ECG), venous plasma norepinephrine (highperformance liquid chromatography), and efferent postganglionic muscle sympathetic nerve activity (microneurography, peroneal nerve). For similar anthropometric and hemodynamic values, renal failure patients displayed muscle sympathetic nerve activity values significantly and markedly greater than controls (60.0Ϯ2.1 versus 45.7Ϯ2.0 bursts per 100 heartbeats; PϽ0.001). Muscle sympathetic nerve activity showed a progressive and significant increase from the first to the fourth quartile of the estimated glomerular filtration rate values (first: 41.0Ϯ2.7; second: 51.9Ϯ1.7; third: 59.8Ϯ3.0; fourth: 61.9Ϯ3.3 bursts per 100 heartbeats), the statistical significance (PϽ0.05) between groups being maintained after adjustment for confounders. In the population as a whole, muscle sympathetic nerve activity was significantly and inversely correlated with the estimated glomerular filtration rate (rϭϪ0.59; PϽ0.0001). Thus, adrenergic activation is a phenomenon not confined to advanced renal failure but already detectable in the initial phases of the disease. The sympathetic overdrive parallels the severity of the renal failure, state and, thus, it might participate, in conjunction with other factors, at the disease progression. (Hypertension. 2011;57:846-851.) Key Words: chronic renal failure Ⅲ microneurography Ⅲ sympathetic nervous system A dvanced renal failure is accompanied by a marked activation of sympathetic cardiovascular influences, as documented by the increase in the circulating plasma levels of norepinephrine, the elevated number of sympathetic neural bursts recorded in the peroneal nerve via the microneurographic technique, and the augmented oscillations in the high-frequency band of the heart rate power spectra. [1][2][3][4][5][6][7][8][9][10][11][12][13] Whether the sympathetic activation also characterizes the earlier clinical phases of the renal failure state is not clear, however. This is because in the few studies performed so far in patients with mild renal disease, the population sample was small, and the plasma levels of norepinephrine showed inconsistent changes. 11,12 Furthermore, in the 2 previously published studies that assessed sympathetic nerve traffic via microneurography, approximately half of the patients evaluated ...

These data suggest that the supine heart rate can be regarded as a marker of intersubject differences in sympathetic tone, and that this is the case both in the general population and in those with cardiovascular diseases. Its value for this purpose is limited, however, and the limitations may be more evident in essential hypertension than in conditions such as obesity and heart failure.

Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 [95% CI, 1.21–1.93]) or CVM (hazard ratio, 2.08 [95% CI, 1.146–2.97]; P <0.001). Cutoff values of SUA able to discriminate total mortality (4.7 mg/dL [95% CI, 4.3–5.1 mg/dL]) and CVM status (5.6 mg/dL [95% CI, 4.99–6.21 mg/dL]) were identified. The information on SUA levels provided a significant net reclassification improvement of 0.26 and of 0.27 over the Heart Score risk chart for total mortality and CVM, respectively ( P <0.001). Sex-specific cutoff values for total mortality and CVM were also identified and validated. In conclusion, SUA levels increasing the risk of total mortality and CVM are significantly lower than those used for the definition of hyperuricemia in clinical practice. Our data provide evidence of a cardiovascular SUA threshold that might contribute in clinical practice to improve identification of patients at higher risk of CVM.

These data provide evidence that, in obese hypertensive individuals, treatment with candesartan cilexetil has an antihypertensive effect similar to that of HCTZ. Unlike diuretic treatment, however, treatment with candesartan cilexetil improves insulin sensitivity and exerts sympathoinhibitory effects.

Abstract-No agreement exists as to the mechanisms responsible for the sympathetic hyperactivity characterizing human obesity, which has been ascribed recently to a chemoreflex stimulation brought about by obstructive sleep apnea rather than to an increase in body weight, per se. In 86 middle-age normotensive subjects classified according to body mass index, waist-to-hip ratio, and apnea/hypopnea index (overnight polysomnographic evaluation) as lean and obese subjects without or with obstructive sleep apnea, we assessed via microneurography muscle sympathetic nerve traffic. The 4 groups were matched for age, gender, and blood pressure values, the 2 obese groups with and without obstructive sleep apnea showing a similar increase in body mass index (32.4 versus 32.0 kg/m 2 , respectively) and waist-to-hip ratio (0.96 versus 0.95, respectively) compared with the 2 lean groups with or without obstructive sleep apnea (body mass index 24.3 versus 23.8 kg/m 2 and waist-to-hip ratio 0.77 versus 0.76, respectively; PϽ0.01). Compared with the nonobstructive sleep apnea lean group, muscle sympathetic nerve activity showed a similar increase in the obstructive sleep apnea lean group and in the nonobstructive sleep apnea obese group (60.4Ϯ2.3 and 59.3Ϯ2.0 versus 40.9Ϯ1.8 bs/100 hb, respectively; PϽ0.01), a further increase being detected in obstructive sleep apnea subjects (73.1Ϯ2.5 bursts/100 heart beats; PϽ0.01). Our data demonstrate that the sympathetic activation of obesity occurs independently in obstructive sleep apnea. They also show that this condition exerts sympathostimulating effects independent of body weight, and that the obstructive sleep apnea-dependent and -independent sympathostimulation contribute to the overall adrenergic activation of the obese state. Key Words: sleep apnea syndromes Ⅲ sympathetic nervous system Ⅲ chemoreceptors Ⅲ baroreflex S ubjects with obesity are characterized by an increase in urinary norepinephrine (NE), plasma levels of NE, efferent postganglionic muscle sympathetic nerve activity (MSNA), and renal NE spillover rate, 1-10 thereby displaying a hyperadrenergic state. This has been ascribed primarily to the insulin-resistance state and the subsequent hyperinsulinemia that occurs more frequently with an increase in body weight because in animals and human, insulin has been shown to stimulate the sympathetic nervous system. [11][12][13][14][15] However, it has also been ascribed to other mechanisms, among which is the chemoreceptor stimulation brought about by obstructive sleep apnea (OSA), 16,17 a condition that is also common in obese individuals. 18 Indeed, OSA has been reported to be the necessary condition for the obesity-related sympathetic hyperactivity to occur in a study by Narkiewicz et al 19 in which an increased number of sympathetic bursts to skeletal muscle tissues was seen only when obesity and OSA were concomitantly present.The present study was conducted to determine the relative contribution of the increased body weight, per se, versus OSA in producing the sympathetic ...