Sympathetic nerve hyperactivity of essential hypertension is lower in postmenopausal women than men

Sympathetic activation has been associated with the development and complications of hypertension. While the prevalence of hypertension and its cardiovascular risks in women are found to be less than in men and tend to become similar to men after the menopause, there have been no data on the level of sympathetic activation in postmenopausal women relative to men. Therefore, we planned to find out whether muscle sympathetic nerve hyperactivity of essential hypertension (EHT) in postmenopausal women is different from that in matched men. We quantified muscle sympathetic nerve activity (MSNA) as mean frequency of single units (s-MSNA) and multiunit bursts (b-MSNA) in 21 postmenopausal women with EHT (W-EHT) relative to 21 matched men with EHT (M-EHT), in comparison to two control groups of 21 normal women (W-NC) and 21 men (M-NC), respectively. The EHT groups had greater MSNA indices than NC groups. W-EHT had lower (P<0.05) s-MSNA (63+/-22.7 impulses per 100 cardiac beats) than M-EHT (78+/-11.2 impulses per 100 cardiac beats). W-NC had lower (P<0.05) s-MSNA (53+/-12.4 impulses per 100 cardiac beats) than M-NC (65+/-16.3 impulses per 100 cardiac beats). Similar results were obtained for b-MSNA. Postmenopausal women with EHT had lower level of central sympathetic hyperactivity than men. Similarly, normal postmenopausal women had lower MSNA than men. These findings suggest that postmenopausal women continue to have a lower sympathetic nerve activity than men even after the development of EHT, and that this could have implications for gender-specific management of hypertension.     

Relationship between central sympathetic activity and stages of human hypertension

BACKGROUND: The magnitude of sympathetic hyperactivity in essential hypertension (EHT) varies with its severity and complications. There are no data on sympathetic nerve activity in borderline (BHT) or white-coat hypertension (WHT) relative to the various stages of EHT, despite suggestions that both lead to established EHT and organ damage through sympathetic mechanisms. We planned to determine the magnitude of sympathetic nerve activity in patients with BHT and WHT in relation to normality and various stages of sustained EHT. METHODS: We examined 90 untreated subjects comprising matched groups with BHT (n = 13), WHT (n = 12), Sixth Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure EHT stage 1 (EHT-1 n = 12), EHT stages 2 and 3 (EHT-2/3 n = 14), high-normal pressure (HN n = 14), and normal pressure (NT n = 13), as well as a group with EHT complicated by left ventricular hypertrophy (EHT+LVH n = 12). We quantified muscle sympathetic nerve activity as the mean frequency of multiunit discharge (MSNA) and that of single-units (s-MSNA). RESULTS: We found a greater (at least P <.01) mean central sympathetic frequency in BHT (75 +/- 5.8 impulses/100 beats), EHT-1 (76 +/- 4.0 impulses/100 beats), and EHT+LVH (79 +/- 4.3 impulses/100 beats) than in EHT-2/3 (57 +/- 3.1 impulses/100 beats), WHT (52 +/- 3.6 impulses/100 beats), HN (42 +/- 3.9 impulses/100 beats), and NT (33 +/- 3.6 impulses/100 beats). BHT hyperactivity was closer to that of EHT, whereas WHT was closer to NT. CONCLUSIONS: Central sympathetic activity was greatest in BHT, early stage, and complicated EHT, and as such is likely to play an integral role in the development of hypertension and its complications. Sympathetic hyperactivity occurs in WHT, but to a lesser extent than in BHT.     

Sympathetic neural mechanisms in white-coat hypertension

OBJECTIVES: This study planned to establish whether sympathetic hyperactivity exists in white-coat hypertension (WHT) in the clinical setting, relative to matched groups with normotension (NT) and untreated essential hypertension (EHT). BACKGROUND: White-coat hypertension differs from EHT by the presence of normal ambulatory blood pressure. Sympathetic hyperactivity exists in patients with EHT in the clinical setting and is believed to contribute to the development of target organ damage. Similar organ damage has been reported in WHT, yet little is known about sympathetic neural activity in this condition. METHODS: Using microneurography, we examined groups of 12 matched subjects with WHT, EHT and NT during the same clinical setting to quantify muscle sympathetic nerve activity as multiunit discharge (MSNA) and single units (s-MSNA). RESULTS: The s-MSNA in WHT (54 +/- 4.2 impulses/100 beats) was greater (p < 0.05) than in NT (37 +/- 5.4 impulses/100 beats) despite similar age and body mass index (BMI). The EHT values of s-MSNA (73 +/- 5.2 impulses/100 beats) were significantly (p < 0.05) greater than in WHT despite similar age, BMI and blood pressure levels. The MSNA followed a similar trend. White-coat hypertension had a similar cardiac baroreceptor reflex sensitivity to NT, but this was impaired in EHT relative to both NT and WHT. CONCLUSIONS: It was shown, in the clinical setting, that central sympathetic hyperactivity exists in WHT, albeit to a lesser degree than EHT. These findings suggest that WHT may not be entirely benign and that the observed sympathetic hyperactivity may be responsible for development of target organ damage in this group of patients.     

Sympathetic neural activation in nondiabetic metabolic syndrome and its further augmentation by hypertension

Hypertension is a major cardiovascular risk factor in the metabolic syndrome (MS) in which the presence of insulin resistance, glucose intolerance, abnormal lipoprotein metabolism, and central obesity all confer an increased risk. Because essential hypertension (EHT), insulinemia, and visceral fat are associated with sympathetic hyperactivity, which is itself known to increase cardiovascular risk, the aim of this study was to see if MS is a state of sympathetic nerve hyperactivity and if the additional presence of EHT intensifies this hyperactivity. In 69 closely matched subjects, comprising hypertensive MS (MS+EHT, 18), normotensive MS (MS-EHT, 17), hypertensives without MS (EHT, 16), and normotensive controls without MS (NC, 18), we measured resting muscle sympathetic nerve activity (MSNA) as assessed from multiunit discharges and from single units with defined vasoconstrictor properties (s-MSNA). The s-MSNA in MS+EHT (76+/-3.1 impulses/100 beats) was greater (at least P<0.01) than in MS-EHT (62+/-3.2 impulses/100 beats) and in EHT (60+/-2.3 impulses/100 beats), and all these were significantly greater (at least P<0.01) than in NC (46+/-2.7 impulse/100 beats). The multi-unit MSNA followed a similar trend. These findings suggest that MS is a state of sympathetic nerve hyperactivity and that the additional presence of hypertension further intensifies this hyperactivity. The degree of sympathetic hyperactivity seen in this study could be argued at least partly to contribute to the higher cardiovascular risk and metabolic abnormalities seen in MS+EHT patients.     

The sympathetic drive after acute myocardial infarction in hypertensive patients

BACKGROUND: Sympathetic activation occurs in hypertension (HT) and after acute myocardial infarction (AMI) and is related to greater cardiovascular risk. Also, AMI in patients with HT (AMI-HT) carries greater risk than that in normal subjects (AMI-NT). We therefore planned to determine whether the sympathetic activation and its duration after AMI are greater in patients with antecedent HT than in patients with normal arterial pressure (NT). METHODS: In 68 matched subjects with uncomplicated AMI-HT (n = 17), AMI-NT (n = 17), HT (n = 17), and NT (n = 17), we measured resting muscle sympathetic nerve activity (MSNA) as the mean frequency of multiunit bursts (m-MSNA) and single units (s-MSNA). In AMI groups data were obtained 2 to 4 days after AMI and then at 3-month intervals until MSNA returned to levels found in HT and NT. RESULTS: The AMI-HT had greater (at least P < 0.05; ANOVA) s-MSNA (99 +/- 3.5 impulses/100 cardiac beats) than AMI-NT (84 +/- 2.8 impulses/100 cardiac beats). During follow up, s-MSNA hyperactivity in AMI-HT was always greater than in AMI-NT, and returned to values found in HT and NT (84 +/- 3.5 impulses/100 cardiac beats and 62 +/- 4.4 impulses/100 cardiac beats, respectively) 9 months after AMI. Similar results were obtained for m-MSNA. CONCLUSIONS: AMI in hypertensives resulted in greater MSNA levels lasting at least 6 months longer than AMI in normotensives. This indicates that AMI further augmented the MSNA hyperactivity of HT and that this could be one mechanism involved in the reported worse prognosis in AMI-HT.     

The effect of gender on the sympathetic nerve hyperactivity of essential hypertension

We planned to determine whether or not there is a difference in the level of muscle sympathetic nerve activity (MSNA) between hypertensive women and hypertensive men. Sympathetic activation of essential hypertension (EHT) has been associated with increased cardiovascular events, which are known to be less likely to occur in women than in men. Normal women have been reported to have less sympathetic nerve activity than men, but no reported data are available regarding gender differences in sympathetic activity in hypertensive subjects. We examined 36 patients with untreated and uncomplicated EHT comprising 18 women and 18 men, and 36 normal controls comprising 18 women and 18 men. MSNA was quantified as the mean frequency of single units and as multiunit bursts using the technique of microneurography. The hypertensive groups had greater sympathetic nerve activity than the control groups. Female hypertensives had lower (P<0.001) single unit hyperactivity (56+/-1.7 impulses/100 cardiac beats) than male hypertensives (72+/-1.7 impulses/100 cardiac beats). Normotensive females had lower (P<0.01) single unit activity (42+/-3.6 impulses/100 cardiac beats) than normotensive males (56+/-4.6 impulses/100 cardiac beats). Similar results were obtained for the frequency of multiunit burst activity. Hypertension in women is associated with a lower level of central sympathetic hyperactivity than in men. It is suggested that this may at least partly explain the observed lower hypertension-related cardiovascular events in women than in men. In addition, the findings may have implications for gender-specific management of hypertension.     

Disparity of autonomic control in type 2 diabetes mellitus

Aims/hypothesis Acute insulinaemia activates the sympathetic drive in a nonuniform manner. The extent and nature of such activation in type 2 diabetic patients who do not have neuropathy have not yet been addressed despite evidence relating sympathetic activation to cardiovascular risk. We planned to determine the magnitude and extent of the sympathetic drive and its reflex responses in patients with type 2 diabetes and fasting hyperinsulinaemia.Methods We measured resting muscle sympathetic nerve activity (MSNA) as the mean frequency of multi-unit bursts and single unit muscle sympathetic nerve activity (s-MSNA) in 17 overweight patients with type 2 diabetes and two matched normal control groups comprising 17 overweight and 16 normal-weight subjects. We also tested the MSNA and s-MSNA responses to cold pressor and isometric hand-grip tests, along with the effect of sympatho-vagal balance on heart period variability.Results Both MSNA and s-MSNA in the group with type 2 diabetes (66±3.5 bursts/100 beats and 78±4.5 impulses/100 beats) were greater (at least p<0.0001) than in the overweight control group (42±2.6 bursts/100 beats and 48±3.4 impulses/100 beats) and normal-weight control group (43±6.2 bursts/100 beats and 51±7.1 impulses/100 beats), though the three groups had similar reflex responses, baroreflex sensitivity and sympatho-vagal balance controlling the heart period.Conclusions/interpretation The patients with type 2 diabetes had no evidence of impaired reflex or autonomic control of heart period variability at a time when there was central sympathetic activation to the periphery. Furthermore, being overweight itself was not associated with sympathetic activation.     

Abnormal muscle metaboreflex control of sympathetic activity in never-treated hypertensive subjects

BACKGROUND: Muscle metaboreflex control in hypertensive subjects has not been described yet. We investigated the integrity of muscle metaboreflex control of muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in never-treated hypertensive subjects. METHODS: Eighteen hypertensive (42+/-1 years) and 22 normotensive subjects (38+/-1 years) were studied. The MSNA was measured by microneurography and forearm blood flow (FBF) by venous occlusion plethysmography. The BP was noninvasively monitored. RESULTS: Baseline MSNA was significantly increased in hypertensive subjects when compared with normal subjects (34+/-2 v 22+/-2 bursts/min, P<.001). Baseline FBF was significantly decreased in hypertensive subjects (2.66+/-0.2 v 2.05+/-0.1 mL/min/100 mL, P=.04). During moderate handgrip exercise (30% maximal voluntary contraction), MSNA levels were significantly higher in hypertensive subjects. However, MSNA responses were significantly lower in hypertensive subjects (1+/-3 v 10+/-2 bursts/100 heart beats, P = .001). Similarly, FBF responses were significantly lower in hypertensive subjects when compared with normotensive subjects (0.70+/-0.19 v 1.60+/-0.36 mL/min/100 mL, P=.04). During the postexercise circulatory arrest, when the metaboreflex control is isolated, MSNA levels returned toward baseline in hypertensive subjects (58+/-4 v 55+/-3 bursts/100 heart beats, P=.98). In contrast, in normotensive subjects, MSNA levels remained significantly elevated when compared with baseline (48+/-3 v 35+/-1 bursts/100 heart beats, P<.001). CONCLUSIONS: These findings suggest an association between hypertension and decreased muscle metaboreflex control of MSNA.     

Arterial pressure lowering effect of chronic atenolol therapy in hypertension and vasoconstrictor sympathetic drive

Although the beta1-adrenergic blocking agent atenolol is an established antihypertensive therapy, its effect on peripheral sympathetic vasoconstrictor drive has remained controversial. In patients with hypertension, atenolol therapy has been reported to either increase or have no effect on peripheral vascular resistance, despite other reports showing no change or a decrease in peripheral sympathetic drive. This study was designed, in patients with untreated essential hypertension (EHT), to quantify changes in simultaneously measured peroneal muscle sympathetic nerve activity (MSNA) and calf vascular resistance (CVR) accompanying atenolol therapy. MSNA was quantified as the mean frequency of single units (s-MSNA) and as multiunit bursts (MSNA bursts) using the technique of microneurography, and CVR was measured using a standard plethysmographic technique. Firstly, by comparing two age- and body weight- matched groups, each of 14 patients with hypertension, we found that the group on atenolol therapy (treated-HT) had similar MSNA values counted over the same number of cardiac beats and similar CVR levels (at least P>0.40) to the group without therapy (untreated-HT). Secondly, we examined 10 EHT patients before and after 8+/-0.4 weeks of oral atenolol therapy (HT-A) in comparison to seven control patients with hypertension and no treatment (HT-C) who were examined over a similar period of time. We found that the measures of MSNA and CVR did not significantly change in both groups. We conclude that the arterial pressure lowering effect of atenolol was not related to significant changes in central vasoconstrictor sympathetic drive to the periphery.     

Adrenergic and reflex abnormalities in obesity-related hypertension

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. 5+/-2.2 years, body mass index 22.8+/-0.7 kg/m(2) [mean+/-SEM]), 16 normotensive obese subjects (body mass index 37.2+/-1.3 kg/m(2)), 13 lean hypertensive subjects (body mass index 24.0+/-0.8 kg/m(2)), and 16 obese hypertensive subjects (body mass index 37.5+/-1.3 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 (P:<0.01) greater in obese normotensive subjects (49.1+/-3.0 bursts per 100 heart beats) and in lean hypertensive subjects (44.5+/-3.3 bursts per 100 heart beats) than in lean normotensive control subjects (32.2+/-2.5 bursts per 100 heart beats); a further increase was detectable in individuals with the concomitant presence of obesity and hypertension (62.1+/-3. 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.     

Sympathetic nerve hyperactivity in non-diabetic offspring of patients with type 2 diabetes mellitus

Aims/hypothesis Type 2 diabetes mellitus with hyperinsulinaemia is a state of sympathetic nerve hyperactivity, which can develop subsequently in non-diabetic first-degree offspring of patients with type 2 diabetes. Although both type 2 diabetes and sympathetic activation are major cardiovascular risk factors, the level of sympathetic nerve activity is as yet unknown in offspring of type 2 diabetic patients who are ostensibly normal. We therefore sought to quantify sympathetic nerve activity and its relationship to plasma insulin levels in ostensibly normal offspring of patients with type 2 diabetes, relative to a matched normal control group with no family history of type 2 diabetes.Subjects and methods In two closely matched groups comprising 23 non-diabetic offspring of type 2 diabetic patients and 23 normal control individuals we measured resting muscle sympathetic nerve activity (MSNA) as the mean frequency of multi-unit bursts of MSNA and single units of MSNA (s-MSNA) with defined vasoconstrictor properties.Results In offspring of type 2 diabetic patients, the fasting plasma levels of insulin (7.4±0.80 μU/ml) and s-MSNA (45±3.2 impulses/100 beats) were greater (p<0.009 and p<0.003) than those in control persons (4.6±0.76 μU/ml and 32±3.1 impulses/100 beats, respectively). MSNA bursts and derived insulin resistance followed similar trends. Sympathetic nerve activity was significantly correlated to insulin levels (p<0.0002) and resistance (p<0.0001) in offspring of type 2 diabetic patients, but not in control subjects.Conclusions/interpretation Sympathetic activation occurred in normal non-diabetic offspring of patients with type 2 diabetes in proportion to their plasma insulin levels. Our data indicate the presence of a mechanistic link between hyperinsulinaemia and sympathetic activation, both of which could play a role in the subsequent development of cardiovascular risk factors.     

Inhibition of awake sympathetic nerve activity of heart failure patients with obstructive sleep apnea by nocturnal continuous positive airway pressure

OBJECTIVES: This study was designed to determine whether reductions in morning systolic blood pressure (BP) elicited by treatment of moderate to severe obstructive sleep apnea (OSA) in heart failure (HF) patients are associated with a reduction in sympathetic vasoconstrictor tone. BACKGROUND: Daytime muscle sympathetic nerve activity (MSNA) is elevated in HF patients with coexisting OSA. In our recent randomized trial in HF, abolition of OSA by continuous positive airway pressure (CPAP) increased left ventricular ejection fraction (LVEF) and lowered morning systolic BP. METHODS: Muscle sympathetic nerve activity, BP, and heart rate (HR) of medically treated HF patients (EF <45%) and OSA (apnea-hypopnea index > or =20/h of sleep) were recorded on the morning after overnight polysomnography, and again one month after patients were randomly allocated nocturnal CPAP treatment or no CPAP (control). RESULTS: In nine control patients, there were no significant changes in the severity of OSA, MSNA, systolic BP, or HR. In contrast, in the 8 CPAP-treated patients, OSA was attenuated, and there were significant reductions in daytime MSNA (from 58 +/- 4 bursts/min to 48 +/- 5 bursts/min; 84 +/- 4 bursts/100 heart beats to 72 +/- 5 bursts/100 heart beats; p < 0.001 and p = 0.003, respectively), systolic BP (from 135 +/- 5 mm Hg to 120 +/- 6 mm Hg, p = 0.03), and HR (from 69 +/- 2 min(-1) to 66 +/- 2 min(-1); p = 0.013). CONCLUSIONS: Treatment of coexisting OSA by CPAP in HF patients lowers daytime MSNA, systolic BP, and HR. Inhibition of increased central sympathetic vasoconstrictor outflow is one mechanism by which nocturnal CPAP reduces awake BP in HF patients with moderate to severe OSA.     

Sympathetic and cardiac baroreflex function in panic disorder

BACKGROUND: Recent reports have demonstrated increased cardiac risk, and an association with essential hypertension in patients with panic disorder. The cause is not known, but possibly involves sympathetic nervous activation. In this study, we evaluated the arterial baroreflex control of vascular sympathetic nervous outflow and cardiac baroreflex function in panic disorder patients. METHODS AND RESULTS: We studied nine patients suffering from panic disorder and ten healthy subjects. Microneurographic recording of muscle sympathetic nerve activity (MSNA) was made with simultaneous recording of blood pressure (BP) and electrocardiogram (ECG). The relationship between MSNA and spontaneous diastolic BP (DBP) changes was assessed at rest and was defined as the arterial baroreflex control of MSNA. Cardiac baroreflex function was assessed using the sequence method. Anxiety was assessed using Spielberger's anxiety state and trait inventory. The slopes of the relationship between MSNA and DBP were more negative (steeper) in the panic disorder group compared with the control subjects (-5.97 +/- 0.45 versus -3.06 +/- 0.43 bursts/100 heart beats per mmHg, P < 0.001). Panic disorder patients had significantly higher state and trait anxiety scores. The slope of the relationship between MSNA and diastolic BP was significantly related to the trait anxiety of the subjects. There was no difference between the cardiac baroreflex sensitivity between the two groups. CONCLUSION: Patients with panic disorder exhibit enhanced reflex gain of the arterial baroreflex control of MSNA but no change in the cardiac baroreflex. While any clinical significance this observation might have in relation to increased cardiac risk in panic disorder, or to concordance with essential hypertension, remains to be elucidated, increased reactivity of vasoconstricting sympathetic nerves may be a trait characteristic in this cohort.     

Reduced sympathoneural responses to the cold pressor test in individuals with essential hypertension and in those genetically predisposed to hypertension. No support for the "pressor reactor" hypothesis of hypertension development

BACKGROUND: The aim of this study was to examine the influences of genetic predisposition to hypertension and of age on the sympathetic nervous system response to the cold pressor test (CPT). METHODS: A total of 32 young subjects (aged 27 +/- 2 years) were studied: 11 normotensive subjects without a family history of hypertension (FH), 14 normotensive subjects with a strong family history of hypertension (FH+), and eight hypertensive subjects. In addition, 21 older subjects (aged 53 +/- 2 years) were studied: 13 hypertensive and eight normotensive subjects. Blood pressure (BP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were recorded at rest and during a 2-min period of a CPT. RESULTS: Both young and older hypertensive subjects had higher resting MSNA than did the normotensive ones (47 +/- 7 v 29 +/- 4 bursts per 100 heartbeats (P < .05) and 66 +/- 4 v 40 +/- 7 bursts per 100 heartbeats (P < .01), respectively). The CPT resulted in HR increases of similar magnitude in all groups of patients. The FH+ group displayed slightly less increase in systolic BP than that of the FH- group (P < .05). The MSNA increased to a far greater degree in FH- (103%) than in FH+ (32%) and in young hypertensive patients (12%) (P < .05). Similarly, MSNA change with the CPT was greater in older normotensive subjects than in older hypertensive patients (61% v 12%, P < .05). CONCLUSIONS: Our results show that a CPT induces sympathetic responses that are subnormal in hypertensive patients and those with a family history of hypertension, highlighting the importance of genetic factors in determining the sympathetic nervous reactivity to CPT.     

Relationship of neurovascular compression to central sympathetic discharge and essential hypertension

OBJECTIVES: We planned to examine the relationship between neurovascular compression (NVC) of the rostral ventrolateral medulla (RVLM) and the magnitude of central sympathetic hyperactivity in normal subjects and in patients with untreated and uncomplicated essential hypertension (EHT). BACKGROUND: Previously it has not been possible to establish a definitive relationship between EHT and NVC of the RVLM, a location containing efferent sympathetic vasoconstrictor neurons. Furthermore, the relationship between NVC and magnitude of sympathetic nerve hyperactivity has not been adequately examined, despite the knowledge that hyperactivity varies according to EHT severity. METHODS: In 83 subjects, we used magnetic resonance imaging to detect NVC and, independently, peroneal microneurography to quantify muscle sympathetic nerve activity (MSNA), expressed as the mean frequency of multi-unit discharge (m-MSNA) and of single units (s-MSNA). Subjects were classified according to arterial pressure values into groups with normal (NT) (n = 24) or high-normal (HN) (n = 14) arterial pressure and mild (EHT-1) (n = 26) or severe (EHT-2/3) (n = 19) EHT. RESULTS: A significantly greater sympathetic activity was found in 23 subjects with NVC, compared with 60 subjects without NVC. The prevalence of NVC and the magnitude of sympathetic hyperactivity were greater in the EHT-1 group (p < 0.05) than in the other three groups. There was no significant difference in confounding variables between the groups. Although increased sympathetic activity was strongly predictive of NVC, this was not significantly related to baroreceptor sensitivity controlling the pulse interval (cardiac baroreceptor reflex sensitivity). CONCLUSIONS: Neurovascular compression of the RVLM may cause central sympathetic activation in normal and hypertensive populations and therefore has significant implications regarding the pathogenesis of EHT.     

Atrial septostomy decreases sympathetic overactivity in pulmonary arterial hypertension

BACKGROUND: We have reported previously that the sympathetic nervous system is activated in patients with pulmonary arterial hypertension (PAH), and that this is only partly explained by a decrease in arterial oxygenation. Possible causes for increased muscle sympathetic nerve activity (MSNA) in patients with PAH include right atrial distension and decreased cardiac output. Both may be improved by atrial septostomy, but this intervention also further decreases arterial oxygenation. In the present study, we wanted to investigate the effect of atrial septostomy on MSNA in patients with PAH. METHODS: We recorded BP, heart rate (HR), arterial O2 saturation (SaO2), and MSNA before and after atrial septostomy in PAH patients (mean [+/- SE] age, 48 +/- 5 years) and in closely matched control subjects. Measurements were also performed after septostomy, while SaO2 was brought to the preprocedure level by supplemental O2 therapy. RESULTS: Compared to the control subjects (n = 10), the PAH patients (n = 11) had a lower mean BP (75 +/- 2 vs 96 +/- 3 mm Hg, respectively; p < 0.001), lower mean SaO2 (92 +/- 1% vs 97 +/- 0%, respectively; p < 0.001), increased mean HR (84 +/- 4 vs 68 +/- 3 beats/min; p < 0.01), and markedly increased mean MSNA (76 +/- 5 vs 29 +/- 2 bursts per minute; p < 0.001). Atrial septostomy decreased mean SaO2 (to 85 +/- 2%; p < 0.001) and mean MSNA (to 69 +/- 4 bursts per minute; p < 0.01), but did not affect HR or BP. Therapy with supplemental O2 did not affect MSNA, BP, or HR. The decrease in MSNA was correlated to the decrease in right atrial pressure (r = 0.62; p < 0.05). CONCLUSIONS: Atrial septostomy in PAH patients decreases sympathetic hyperactivity despite an associated decrease in arterial oxygenation, and this appears to be related to decreased right atrial distension.     

Cigarette smoking augments sympathetic nerve activity in patients with coronary heart disease

It has been shown that cigarette smoking increases blood pressure (BP) and heart rate (HR), and decreases muscle sympathetic nerve activity (MSNA) in healthy young smokers. The decrease in MSNA might be secondary to baroreflex responses to the pressor effect. We tested the hypothesis that cigarette smoking increases MSNA in smokers with impaired baroreflex function. The effects of cigarette smoking on BP, HR, forearm blood flow (FBF), forearm vascular resistance (FVR), and MSNA were examined in 14 patients with stable effort angina (59+/-3 years, group CAD) and 10 healthy smokers (23+/-1 years, group C). In group CAD, the arterial baroreflex sensitivity (BRS) was significantly lower than in group C (4.7+/-0.8 versus 15.1+/-2.2 msec/mmHg, P<0.01). In both groups, cigarette smoking increased the plasma concentration of nicotine, systolic and diastolic BP, HR, and FVR significantly (P<0.01), but decreased FBF significantly (P<0.01). After smoking, MSNA was decreased significantly in group C (from 35.2+/-3.5 to 23.5+/-3.2 bursts/100 beats, P<0.01), but increased significantly in group CAD (from 48.8+/-5.4 to 57.3+/-5.5 bursts/100 beats, P<0.01). There was significant correlation between BRS and changes in MSNA (r= -0.62, P<0.01). Cigarette smoking increased MSNA in smokers with impaired baroreflex function. This demonstrates that cigarette smoking stimulates sympathetic nerve activity by both a direct peripheral effect and a centrally mediated effect.     

Sympathetic rhythmicity in cardiac transplant recipients

BACKGROUND: Variability of R-R interval and muscle sympathetic nerve activity (MSNA) occurs predominantly at a low frequency (LF, +/-0.1 Hz) and a high frequency (HF, +/-0.25 Hz) in normal humans. Increased sympathetic drive in normal humans is associated with an increased LF component of the R-R interval and MSNA. Patients with severe heart failure have high sympathetic activity but decreased or absent LF power of both R-R and MSNA. We tested the hypothesis that this dysfunction in autonomic modulation in heart failure can be reversed by heart transplantation. METHODS AND RESULTS: We performed spectral analysis of resting MSNA, R-R interval, and respiration in 9 patients with heart transplants, 9 chronic heart failure patients, and 9 normal control subjects, all closely matched for age, sex, and body mass index. MSNA (bursts per minute) was higher in patients with heart transplants (74+/-3) than either patients with heart failure (56+/-6) or normal subjects (40+/-4) (P<0.001). LF variability in the R-R interval was reduced in both heart transplant recipients and heart failure patients compared with the control subjects (P<0.01). The LF variability in MSNA was also nearly absent in the heart failure patients (P<0.01). However, the LF and HF oscillations in MSNA in patients with heart transplants were comparable to those evident in the control subjects. CONCLUSIONS: Cardiac transplantation does not reduce MSNA. However, LF oscillations in sympathetic activity are restored after transplantation such that the MSNA oscillatory profile is similar to that observed in normal subjects.     

Muscle sympathetic nerve activity during wakefulness in heart failure patients with and without sleep apnea

Sympathetic activation and sleep apnea are present in most patients with symptomatic systolic heart failure (HF). Acutely, obstructive and central apneas increase muscle sympathetic activity (MSNA) during sleep by eliciting recurrent hypoxia, hypercapnia, and arousal. In obstructive sleep apnea patients with normal systolic function, this increase persists after waking. Whether coexisting sleep apnea augments daytime MSNA in HF is unknown. We tested the hypothesis that its presence exerts additive effects on MSNA during wakefulness. Overnight sleep studies and morning MSNA recordings were performed on 60 subjects with ejection fraction <45%. Of these, 43 had an apnea-hypopnea index > or =15 per hour. Subjects with and subjects without sleep apnea were similar for age, ejection fraction, HF etiology, body mass index, blood pressure, and heart rate. Daytime MSNA was significantly higher in those with sleep apnea (76+/-2 versus 63+/-4 bursts per 100 heartbeats [mean+/-SEM], P=0.005; 58+/-2 versus 50+/-3 bursts/min, P=0.037), irrespective of its etiology (the mean difference for central sleep apnea was 17 bursts per 100 heartbeats; n=14; P=0.006; and for obstructive sleep apnea, 11 bursts per 100 heartbeats; n=29; P=0.032). In a subgroup (n=8), treatment of obstructive sleep apnea lowered MSNA by 12 bursts per 100 heartbeats (P=0.003). Convergence of independent excitatory influences of HF and sleep apnea on central sympathetic neurons results in higher MSNA during wakefulness in HF patients with coexisting sleep apnea. This additional stimulus to central sympathetic outflow may accelerate the progression of HF; its attenuation by treatment of sleep apnea represents a novel nonpharmacological opportunity.     

Sympathetic hyperactivity in hypertensive chronic kidney disease patients is reduced during standard treatment

Standard treatment in chronic kidney disease (CKD) patients includes an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. CKD is often characterized by sympathetic hyperactivity. This study investigates the prevalence of sympathetic hyperactivity (quantified by assessment of muscle sympathetic nerve activity [MSNA]) in a sizable group of patients with CKD and assessed whether chronic angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker normalizes increased MSNA. In 74 CKD patients (creatinine clearance 54+/-31 mL/min), MSNA, blood pressure, and plasma renin activity were measured in the absence of antihypertensive drugs except for diuretics. In a subgroup of 31 patients, another set of measurements was obtained after > or =6 weeks of enalapril (10 mg PO), losartan (100 mg PO), or eprosartan (600 mg PO). Patients as compared with control subjects (n=82) had higher mean arterial pressure (113+/-13 versus 89+/-7 mm Hg), MSNA (31+/-13 versus 19+/-7 bursts per minute), and log plasma renin activity (2.67+/-036 versus 2.40+/-0.32 fmol/L per second; all P<0.001). During angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker therapy (n=31), mean arterial pressure (115+/-11 to 100+/-9 mm Hg) and MSNA (33+/-11 to 25+/-9 bursts per minute) decreased (both P<0.01) but were still higher than in control subjects (both P<0.01). Multiple regression analysis identified age and plasma renin activity as predictive for MSNA. In conclusion, sympathetic hyperactivity occurs in a substantial proportion of hypertensive CKD patients. Angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker treatment reduces but does not normalize MSNA.