We examined in 11 young subjects (age 29.7±3.6 years, mean±SEM) whether carotid baroreceptor stimulation via the neck chamber device may affect central venous pressure (CVP), thus potentially ...involving other reflexogenic areas in the examined responses. Application of progressively greater neck chamber subatmospheric pressures caused a progressive lengthening in RR interval, which reached a peak at the maximal value of negative neck chamber pressure applied. This was accompanied by significant and progressively greater reduction in CVP values when the data were calculated considering the early changes occurring within the first 2 seconds of the stimulus. There was a weak correlation between the early changes in CVP and the RR interval responses when all stimuli were pooled together (r = 0.32, P < .05). The results of the present study suggest that the neck chamber technique employed to assess carotid baroreceptor‐heart rate sensitivity can transiently affect via the CVP reduction cardiopulmonary receptors activity, which may participate at the integrated reflex responses.
Although animal models of hypertension have clearly shown that high blood pressure is associated with and is probably caused by an increase in sympathetic cardiovascular influences, a similar ...demonstration in humans has been more difficult to obtain for methodological reasons. There is now evidence, however, of increased sympathetic activity in essential hypertension. This article will review this evidence by examining data showing that plasma norepinephrine is increased in essential hypertension and that this is also the case for systemic and regional norepinephrine spillover, as well as for the sympathetic nerve firing rate in the skeletal muscle nerve district. Evidence will also be provided that sympathetic activation is a peculiar feature of essential hypertension, particularly in its early stages, with secondary forms of high blood pressure not usually characterized by an increased central sympathetic outflow. Humoral, metabolic, reflex, and central mechanisms are likely to be the factors responsible for the adrenergic activation characterizing hypertension, which may also promote the development and progression of the cardiac and vascular alterations that lead to hypertension-related morbidity and mortality, independent of blood pressure values. This represents the rationale for considering sympathetic deactivation one of the major goals of antihypertensive treatment.
Haemochromatosis (HH) displays a number of circulatory alterations concurring at increase cardiovascular risk. Whether these include sympathetic abnormalities in unknown.
In 18 males with primary HH ...(age: 42.3 ± 10.4 years, mean ± SD), clinic and beat-to-beat blood pressure (BP, Finapres), heart rate (HR, EKG), and muscle sympathetic nerve activity (MSNA, microneurography) traffic were measured in the iron overload state and after iron depletion therapy. Haemochromatosis patients displayed elevated serum iron indices while other haemodynamic and metabolic variables were superimposable to ones seen in 12 healthy subjects (C). Muscle sympathetic nerve activity was significantly greater in HH than C (64.8 ± 13.3 vs. 37.8 ± 6.7 bs/100 hb, P < 0.01). Iron depletion caused a significant reduction in serum ferritin, transferrin saturation, and MSNA (from 64.8 ± 13.3 to 39.2 ± 9.2 bs/100 hb, P < 0.01) and a significant improvement in baroreflex-MSNA modulation. This was paralleled by a significant increase in the high-frequency HR variability and by a significant reduction in the low-frequency systolic BP variability components. Before after iron depletion therapy, MSNA was significantly and directly related to transferrin saturation, liver iron concentration, and iron removed, while the MSNA reductions observed after the procedure were significantly and inversely related to the baroreflex-MSNA increases detected after iron depletion. In C, all variables remained unchanged following 1 month observation.
These data provide the first evidence that in HH iron overload is associated with an hyperadrenergic state and a baroreflex alteration, which are reversed by iron depletion. These findings underline the importance of iron overload in modulating sympathetic activation, possibly participating at the elevated cardiovascular risk reported in HH.
Obese persons are at increased cardiovascular risk and exhibit increased arterial stiffness and impaired endothelial function of large- and medium-size arteries. We hypothesized that normotensive ...subjects suffering from severe obesity would also present remodeling and endothelial dysfunction of small resistance arteries. A total of 16 lean (age: 49.6 ± 2.9 years, BMI: 22.9 ± 0.3 kg/m2, mean ± s.e.m.) and 17 age-matched severely obese (BMI: 41.1 ± 2.3 kg/m2) normotensive subjects were investigated. None had glucose or lipid metabolic abnormalities except for insulin resistance. Resistance arteries, dissected from abdominal subcutaneous tissue, were assessed on a pressurized myograph. For superimposable blood pressure, the media thickness, media cross-sectional area (CSA), and media-to-lumen ratio values of resistance arteries were markedly and significantly greater in obese compared to lean subjects (media thickness 26.3 ± 0.6 vs. 16.2 ± 0.6 µm, CSA 22,272 ± 1,339 vs. 15,183 ± 1,186 µm2, and media-to-lumen ratio 0.113 ± 0.006 vs. 0.059 ± 0.001, respectively, P < 0.01). Acetylcholine-induced relaxation was impaired in vessels from obese subjects compared to the lean individuals (−40.4 ± 1.3%, P < 0.01), whereas endothelium-independent vasorelaxation was similar in all groups. Stiffness of small arteries as assessed by the stress/strain relationship was similar in lean and severely obese subjects. We conclude that severe human obesity is associated with profound alterations in structural and functional characteristics of small arteries, which may be responsible for the presence of elevated cardiovascular risk and increased incidence of coronary, cerebrovascular and renal events reported in obesity.
A number of cardiovascular disease have been shown to be characterized by a marked increase in sympathetic drive to the heart and the peripheral circulation. This is the case for essential ...hypertension, congestive heart failure, cardiac arrhythmias, obesity, metabolic syndrome, obstructive sleep apnea, and chronic renal disease. 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 in the pathogenesis of hypertension-related target organ damage. It also reviews the role of sympathetic neural factors in the development of cardiovascular diseases not necessarily strictly related to the hypertensive state, such as congestive heart failure, cardiac arrhythmias, obesity, metabolic syndrome and renal failure. The paper will finally review the pharmacological and non-pharmacological interventions acting on the sympathetic drive. Emphasis will be given to the new approaches, such as renal nerves ablation and carotid baroreceptor stimulation, which have been shown to exert sympathoinhibitory effects.
Sympathetic overactivity and high levels of the endogenous inhibitor of NO synthase asymmetric dimethylarginine (ADMA) are prevalent risk factors in chronic kidney disease (CKD).
In 48 stage 2 to 4 ...CKD patients, we investigated the relationship between efferent postganglionic muscle sympathetic nerve traffic (microneurography) and circulating ADMA and analyzed the links between these risk factors and estimated GFR (eGFR), proteinuria, and different parameters of left ventricular (LV) geometry.
CKD patients characterized by sympathetic nerve traffic values in the third tertile showed the highest ADMA levels, and this association was paralleled by a continuous, positive relationship between these two risk factors (r = 0.32, P = 0.03) independent of other confounders. Both sympathetic nerve traffic and ADMA were inversely related to eGFR and directly to proteinuria and LV geometry. Remarkably, the variance of eGFR, proteinuria, and LV geometry explained by sympathetic nerve traffic and ADMA largely overlapped because sympathetic nerve traffic but not ADMA was retained as a significant correlate of the eGFR (P < 0.001) and of the relative wall thickness or the left ventricular mass index/LV volume ratio (P = 0.05) in models including both risk factors. ADMA, but not sympathetic nerve traffic, emerged as an independent correlate of proteinuria (P = 0.003) in a model including the same covariates.
Sympathetic activity and ADMA may share a pathway leading to renal disease progression, proteinuria, and LV concentric remodeling in CKD patients.
Sympathetic activation characterizes essential hypertension, contributing to the development and progression of the high blood pressure state. Throughout the years, evidence has been accumulated to ...show that adrenergic overdrive also participates in the pathogenesis of the end-organ damage associated with hypertension, including cardiac hypertrophy, left ventricular diastolic dysfunction, and heart failure, as well as the vascular structural and functional alterations that frequently can be detected in large, medium-size, and small arteries. Adrenergic overdrive also participates in the renal insufficiency and failure that may accompany the clinical course of the hypertensive state. This paper reviews evidence collected over the past few years documenting the importance of neurogenic factors in the development and progression of end-organ damage. The therapeutic implications of this evidence are also highlighted.
Abstract Alterations in glucose and lipid metabolism frequently cluster with overweight, obesity as well as hypertension in the clinical condition known as metabolic syndrome . The “cardiometabolic ...clustering” is characterized by well-known alterations that increase cardiovascular risk profile such as insulin-resistance, endothelial dysfunction, arterial stiffening, cardiac hypertrophy, and sympathetic activation. The present article will review the evidence collected throughout by years that an increase in the different markers of adrenergic drive, such as plasma norepinephrine and muscle sympathetic nerve traffic, characterizes this condition. Frequently, the increase also involves heart rate, as documented by the results of different epidemiological studies, such as the Pressioni Arteriose Monitorate E Loro Associazioni, in which an increase in heart rate has been shown in patients with metabolic syndrome, in which this hemodynamic parameter has been assessed in the doctor's office, at home, or during the 24-hour period. Finally, current findings suggest that in metabolic syndrome heart rate displays a significant correlation with other indirect and direct adrenergic markers. Taken together, these findings reinforce the concept that drugs used in the metabolic syndrome should exert sympathoinhibitory effects.
Patients with hypertension exhibit an increased sympathetic activity. No information exists as to whether this is the case in normotensive individuals in whom there is an increased ambulatory blood ...pressure, a condition termed “masked” hypertension. We studied 18 middle-aged subjects with masked hypertension in whom we measured muscle sympathetic nerve traffic (peroneal nerve and microneurography) and beat-to-beat arterial blood pressure at rest and during baroreceptor deactivation and activation. Measurements also included anthropometric values and insulin sensitivity (homeostasis model assessment index). Data were compared with those of 20 normotensive subjects, 18 subjects with white-coat hypertension, and 20 patients with “in-office” and “out-of-office” hypertension. All of the individuals were pharmacologically untreated and age-matched with subjects with masked hypertension. Patients with in- and out-of-office and white-coat hypertension displayed resting sympathetic nerve activity values significantly greater than normotensive subjects (75.8±2.5 and 70.8±2.2 versus 45.5±2.0 bursts per 100 heartbeats respectively; P<0.01). This was the case also for masked hypertension (73.5±2.4 bursts per 100 heartbeats; P<0.01), the degree of the sympathetic activation being similar for magnitude to that seen in the other 2 hypertensive conditions. Compared with normotensive subjects, baroreflex-heart rate control was significantly attenuated in all of the hypertensive states, whereas baroreflex-sympathetic control was unaffected. Homeostasis model assessment index was increased in patients with in- and out-of-office and white-coat hypertension, with a further increase in masked hypertension and a direct relation with resting sympathetic nerve traffic (r=0.46; P<0.01). These data provide the first evidence that masked hypertension is characterized by a marked sympathetic overdrive. They further show that the neurogenic alterations are coupled with metabolic and baroreflex abnormalities.
Experimental and clinical studies have clearly shown the role of the sympathetic nervous system in the pathophysiology of several cardiovascular and non-cardiovascular diseases. This short review ...will be aimed at focusing and discussing the new information collected on two specific clinical conditions such as obesity and metabolic syndrome. The paper will briefly describe the four main mechanisms that represent the common link between these two pathophysiological conditions and that through the sympathetic nervous system contribute to increase the cardiovascular risk.
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