Previous studies have shown that sympathetic cardiovascular outflow is increased in obese normotensive subjects and that this increase is associated with a baroreflex impairment. The purpose of this ...study was to determine whether these abnormalities are irreversible or can be favorably affected by body weight reduction.
In 20 obese normotensive subjects (age, 31.3+/-1.7 years; body mass index, 37.6+/-0.9 kg/m2, mean+/-SEM), we measured beat-to-beat arterial blood pressure (Finapres technique), heart rate (ECG), postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve), and venous plasma norepinephrine (high-performance liquid chromatography) at rest and during baroreceptor stimulation and deactivation induced by increases and reductions of blood pressure via stepwise intravenous infusions of phenylephrine and nitroprusside. Measurements were repeated in 10 subjects after a 16-week hypocaloric diet with normal sodium content (4600 to 5000 J and 210 mmol NaCl/d) and in the remaining 10 subjects after a 16-week observation period without any reduction in the caloric intake. The hypocaloric diet significantly reduced body mass index, slightly reduced blood pressure, and caused a significant and marked decrease in both muscle sympathetic nerve activity (from 50.0+/-5.1 to 32.9+/-4.6 bursts per 100 heart beats, P<.01) and plasma norepinephrine (from 356.2+/-43 to 258.4+/-29 pg/mL, P<.05). This was associated with a significant improvement in the sensitivity of the baroreceptor heart rate (+71.5 +/- 11%, P<.01) and muscle sympathetic nerve activity (+124.5 +/- 22%, P<.001) reflex. Total body glucose uptake also increased significantly (+60.8 +/- 12.0%, P<.05), indicating an increase in insulin sensitivity. All variables remained unchanged in subjects not undergoing caloric restriction.
In obese normotensive subjects, a reduction in body weight induced by a hypocaloric diet with normal sodium content exerts a marked reduction in sympathetic activity owing to central sympathoinhibition. This can be due to the consequences of an increased insulin sensitivity but also to a restoration of the baroreflex control of the cardiovascular system with weight loss.
The two novel approaches recently introduced for the treatment of resistant hypertension, i.e. carotid baroreceptor stimulation and renal denervation, share a number of similarities but are also ...characterized by important differences. The similarities include the evidence that both interventions have as common pathophysiological background the state of sympathetic overdrive characterizing essential hypertension. In addition both procedures 1) are invasive, 2) exert in the short-term period clearcut blood pressure lowering effects and 3) still face a number of open questions, particularly related to the long-term blood pressure lowering effects, impact on end-organ damage and on cardiovascular events. The differences include the fact that two procedures act on distinct targets that trigger sympathetic activation and consequently blood pressure increase. In addition, only in the case of carotid baroreceptor stimulation the blood pressure effects can be easily assessed immediately following the implantation. Finally, the economic costs, metabolic effects and impact on vagal modulation of heart rate are different between the two interventions. This paper will provide a comparison of the background, effects and outcome of renal denervation and carotid baroreceptor stimulation, stressing whenever possible the clinical implications of the main features of the two interventions.
In essential hypertension, marked restrictions in dietary sodium intake cause in the short-term period an increase in muscle sympathetic nerve traffic (MSNA) and a baroreflex impairment. The present ...study was set out to assess on a long-term basis the neuroadrenergic and reflex effects of moderate sodium restriction.
In 11 untreated mild to moderate essential hypertensive patients (age 42.0+/-2.6 years, mean+/-SEM), we measured beat-to-beat blood pressure (Finapres), heart rate (ECG), and MSNA (microneurography) at rest and during stepwise intravenous infusions of phenylephrine and nitroprusside. Measurements were performed at regular sodium intake, after 1 and 8 weeks of low-sodium diet (80 mmol NaCl/d), and repeated again at regular sodium intake. After 1 week, urinary sodium excretion was markedly reduced. This was accompanied by a slight blood pressure reduction, no heart rate change, and a significant increase in plasma renin activity, aldosterone, and MSNA (+23.0+/-4.6% P<0.05). Whereas baroreflex heart-rate control was unchanged, baroreflex modulation of MSNA was reduced by 46.8+/-5.1% (P<0.01). At the end of the 8-week low-sodium diet, the neurohumoral and baroreflex responses were similar to the ones observed after 1 week of the dietary intervention. All changes disappeared when regular sodium diet was restored.
Thus, a moderate dietary sodium restriction triggers a sympathetic activation and a baroreflex impairment. Maintenance of low-sodium diet for several weeks does not attenuate these adverse adrenergic and reflex effects.
Indirect and direct approaches to assess sympathetic neural function in man have shown that congestive heart failure is characterized by a marked adrenergic overdrive. Although compensatory in the ...initial phases of the disease, with time the sympathetic overactivity exerts adverse cardiovascular effects, favoring the disease progression and promoting the occurrence of non-fatal and fatal cardiovascular events. This explains why the adrenergic overactivity has become an important target of the therapeutic interventions adopted in the managementof the disease. The present paper will examine the impact of therapeutic approaches, used in the management of heart failure, on the sympathetic activation characterizing the disease. After a brief mention of the sympathetic effects of non-pharmacological interventions and procedural approches, particular emphasis will be given to the effects of pharmacological interventions and device treatments (renal denervation and carotid baroreceptor stimulation), which became in recent years a promising tool for the management of the disease. The clinical implications as well as the unsolved aspects related to the sympathomodulatory interventions in heart failure management will be finally discussed.
•Sympathetic activation characterizes heart failure worsening prognosis.•Drugs currently employed in the treatment of the disease may affect the sympathetic overactivity.•Device-based interventions have been shown to exert favorable effects on sympathetic overactivity.
Nerve traffic recordings (muscle sympathetic nerve traffic MSNA) have shown that sympathetic activation may occur in obesity. However, the small sample size of the available studies, presence of ...comorbidities, heterogeneity of the subjects examined represented major weaknesses not allowing to draw definite conclusions. This is the case for the overweight state. The present meta-analysis evaluated 1438 obese or overweight subjects recruited in 45 microneurographic studies. The analysis was primarily based on MSNA quantification in obesity and overweight, excluding as concomitant conditions hypertension, metabolic syndrome, and other comorbidities. Assessment was extended to the relationships of MSNA with other neuroadrenergic markers, such as plasma norepinephrine and heart rate, anthropometric variables, as body mass index, waist-to-hip ratio, presence/absence of obstructive sleep apnea, and metabolic profile. Compared with normoweights MSNA was significantly greater in overweight and more in obese individuals (37.0±4.1 versus 43.2±3.5 and 50.4±5.0 burts/100 heartbeats, P<0.01). This was the case even in the absence of obstructive sleep apnea. MSNA was significantly directly related to body mass index and waist-to-hip ratio (r=0.41 and r=0.64, P<0.04 and <0.01, respectively), clinic blood pressure (r=0.68, P<0.01), total cholesterol, LDL (low-density lipoprotein) cholesterol, and triglycerides (r=0.91, r=0.94, and r=0.80, respectively, P<0.01) but unrelated to plasma insulin, glucose, and homeostatic model assessment for insulin resistance. No significant correlation was found between MSNA, heart rate, and norepinephrine. Thus, obesity and overweight are characterized by sympathetic overactivity which mirrors the severity of the clinical condition and reflects metabolic alterations, with the exclusion of glucose/insulin profile. Neither heart rate nor norepinephrine appear to represent faithful markers of the muscle sympathetic overdrive.
Scanty information is available on the effects of combination drug treatment based on an ACE inhibitor and a calcium channel blocker on the neurometabolic alterations characterizing obesity-related ...hypertension (OHT). After 2-week run-in with enalapril (20 mg), 36 OHTs were randomized according to a double-blind crossover design to a combination therapy with either lercanidipine 10 mg (L) or felodipine extended release 5 mg (F), each lasting 8 weeks. Measurements included clinic and ambulatory blood pressure (BP) and heart rate, homeostasis model assessment index, plasma norepinephrine, and muscle sympathetic nerve activity. Patients with uncontrolled BP were then uptitrated to 20 mg/d (L) and 10 mg/d (F) combined with enalapril 20 mg, respectively, for further 8 weeks. For similar BP reductions, enalapril-lercanidipine (EL) caused norepinephrine and MSNA increases significantly less pronounced than those seen with enalapril-felodipine, the lesser sympathoexcitation observed with EL being coupled with a significant improvement in homeostasis model assessment index. This was the case also when L and F were uptitrated in the combination. In OHT, at variance from enalapril-felodipine, EL combination is almost entirely devoid of any major sympathoexcitatory effect and is associated with an improvement in insulin sensitivity.
Human aging is characterized by a marked increase in muscle sympathetic nerve traffic (MSNA). No information exists, however, on the effects of aging on skin sympathetic nerve traffic (SSNA) and on ...its reflex modulation by thermoregulatory mechanisms.
In 13 young, 11 middle-aged, and 12 elderly healthy subjects, we measured arterial blood pressure (Finapres), skin temperature (thermocouples), and resting MSNA and SSNA (microneurography). Measurements also included the SSNA responses to (1) an acute increase and reduction (+/-8 degrees C) in room temperature, each lasting 45 minutes and (2) an acoustic stimulus capable to trigger an emotional arousal. Although resting MSNA was progressively and significantly (P<0.05) increased from young to middle-aged and elderly groups, SSNA was significantly (P<0.05) reduced in the latter compared with the former 2 groups. Cold exposure induced a SSNA increase that was significantly (P<0.01) smaller in the elderly than in young and middle-aged subjects. Conversely, heat exposure induced a SSNA reduction that was significantly (P<0.05) smaller in elderly than in young and middle-aged subjects. Compared with SSNA in young individuals, the SSNA change from cold to warm temperature was reduced by 61% in the elderly group. This was not the case, however, for the SSNA responses to the arousal stimulus, which were superimposable in the 3 groups.
These data provide the first demonstration of a dichotomy in the MSNA and SSNA responses to aging. They also show that aging markedly impairs thermoregulatory control of SSNA and that this impairment might participate at the age-related SSNA decrease.
PURPOSE OF REVIEWA number of cardiovascular disease have been shown to be characterized by a marked increase in sympathetic drive to the heart and peripheral circulation. This is the case for ...essential hypertension, congestive heart failure, obesity, metabolic syndrome and chronic renal failure. This review focuses on the most recent findings documenting the role of sympathetic neural factors in the development and progression of the hypertensive state as well as of target organ damage. It also reviews the participation of sympathetic neural factors in the development of the earlier stages of renal failure.
RECENT FINDINGSA marked increase in sympathetic neural discharge, as assessed via the microneurographic technique, has been shown to occur in the predialytic stage of chronic renal failure. Recent evidence, however, indicates that also in the earlier clinical phases of kidney disease, sympathetic activation is detectable. Further data show that sympathetic neural mechanisms participate in renal and/or hypertensive disease progression, favouring the development of target organ damage. Finally, recent findings indicate that the metabolic disarray frequently complicating the high blood pressure state (metabolic syndrome, dislipidemia, insulin resistance) may have as pathophysiological background a sympathetic overdrive. Altogether these data represent the rationale for employing in hypertension (and particularly in resistant hypertension) therapeutic interventions such as carotid baroreceptor stimulation and renal denervation, capable of exerting sympathoinhibitory effects.
SUMMARYThe sympathetic nervous system represents a major pathophysiological hallmark of both hypertension and renal failure and is an important target for the therapeutic intervention.
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