Heart rate variability in intensive care unit patients with delirium.

Sympathovagal balance, assessed with heart rate variability (HRV), may be altered in intensive care unit (ICU) delirium. HRV was measured in the frequency domain [low frequencies (LF)=0.04-0.15 Hz and high frequencies (HF)=0.15-0.40 Hz] with HF in normalized units (HFnu) to evaluate parasympathetic tone and LF:HF ratio for sympathovagal balance. The authors assessed 726 ICU patients and excluded patients with conditions affecting HRV. No difference could be found between patients with (N=13) and without (N=12) delirium by comparing the mean (±standard deviation) of the HFnu (75±7 versus 68±23) and the LF:HF ratio (-0.7±1.0 versus -0.1±1.1). This study suggests that autonomic function is not altered in ICU delirium.

Aliskiren reduces sympathetic nerve activity and blood pressure in chronic kidney disease patients.

BACKGROUND: Hypertensive chronic kidney disease (CKD) patients often have sympathetic hyperactivity. In this pilot study, we evaluated the effect of 6 weeks treatment with aliskiren on sympathetic activity in hypertensive Stages 2-4 CKD patients. METHODS: In 10 CKD patients (8 males, aged 44 ± 11 years, estimated glomerular filtration rate ( 57 ± 22 mL/min/1.73 m(2)), blood pressure and sympathetic activity [quantified by assessment of muscle sympathetic nerve activity (MSNA)] were assessed, while taken off renin-angiotensin blocker, and during the 6 weeks of treatment with aliskiren 300 mg/day. Ten other CKD patients served as control and were studied twice with an interval of 6 weeks without any change in medication, to quantify within subject reproducibility. RESULTS: In the aliskiren study group, MSNA was reduced from 36 ± 8 to 26 ± 8 bursts/min (P = 0.01). Aliskiren lowered supine systolic and diastolic blood pressure from 147 ± 10 to 120 ± 8 and from 96 ± 7 to 83 ± 7 mmHg, respectively (both P < 0.05). MSNA changed in patients treated with aliskiren [-9.6 bursts/min with 95% confidence interval (CI) -4.0 to -15.0; P-value = 0.003] but not in controls (-0.7 bursts/min with 95% CI -2.2 to 4.0; P-value = 0.6). The mean difference in change between aliskiren group and the control group was -8.9 with 95% CI of -15 to -3; P = 0.005. CONCLUSION: In hypertensive CKD patients, 6 weeks aliskiren treatment lowers blood pressure and MSNA (Clinical trial government identifier number: NCT00719316).

Endovascular baroreflex amplification and the effect on sympathetic nerve activity in patients with resistant hypertension: A proof-of-principle study.

BACKGROUND: First in human studies suggest that endovascular baroreflex amplification (EVBA) lowers blood pressure (BP). To explore potential mechanisms for BP reduction, this study examines the effects of EVBA on muscle sympathetic nerve activity (MSNA) and baroreceptor sensitivity (BRS). METHODS: In a single-center sub-study of the CALM-DIEM study (Controlling And Lowering blood pressure with the MobiusHD-Defining Efficacy Markers), 14 patients with resistant hypertension were treated with EVBA. Microneurography and non-invasive continuous BP measurements were performed at baseline and three months after MobiusHD implantation. The primary outcome was change in MSNA. Secondary outcomes were change in baroreflex sensitivity (BRS), cardiovascular responses to a sympathetic stimulus, BP, heart rate (HR) and heart rate variability (HRV). RESULTS: The primary endpoint was obtained in 10 of 14 patients enrolled in the sub-study. MSNA burst frequency and burst incidence decreased in 6 of 10 patients: mean change -4.1 bursts/min (95% confidence interval -12.2 to 4.0) and -3.8 bursts/100 heartbeats (-15.2 to 7.7). MSNA spike frequency and spike count decreased in 8 of 10 patients: mean change -2.8 spikes/sec (-7.3 to 1.8) and -3.0 spikes/heartbeat (-6.1 to 0.1). Change in MSNA and BP were not correlated. Office BP decreased by -14/-6 mmHg (-27 to -2/-15 to 3). We observed a trend towards decreased HR (-5 bpm, -10 to 1) and increased total power HRV (623 msec2, 78 to 1168). In contrast, BRS and cardiovascular responses remained unchanged after EVBA. CONCLUSIONS: In this proof-of-principle study, EVBA did not significantly decrease MSNA in patients with resistant hypertension. EVBA did not impair baroreflex function. TRIAL REGISTRATION: Clinical trial registration at NCT02827032.

Sympathetic activity in chronic kidney disease patients is related to left ventricular mass despite antihypertensive treatment.

BACKGROUND: Chronic kidney disease (CKD) patients often have sympathetic hyperactivity, which contributes to the pathogenesis of hypertension and cardiovascular organ damage. Angiotensin-converting enzyme (ACE) inhibitors (ACEi) and angiotensin II receptor blockers (ARB) reduce sympathetic hyperactivity. Ideally, treatment should eliminate the relation between sympathetic activity and organ damage. The aim of the present study is firstly to compare left ventricular mass (LVM) of CKD patients using chronic ACEi or an ARB with LVM of controls. Secondly, we determine whether previously found muscle sympathetic nerve activity (MSNA) and arterial blood pressure during follow-up are predictive for the presence of increased LVM. Methods. We restudied 20 CKD patients and 30 healthy volunteers matched for age. Sympathetic nerve activity was quantified by the microneurography (MSNA). Arterial blood pressure was the mean of office blood pressure measurements. LVM was quantified by magnetic resonance imaging (MRI) without contrast. RESULTS: The period between MSNA and MRI measurements was 9 ± 3 years. All patients were treated according to guidelines with an ACEi or an ARB. In CKD patients, mean systolic and diastolic arterial pressure were 129 ± 10 and 84 ± 5 mmHg, respectively, during follow-up. In patients, as compared to controls, LVM was 93 ± 16 versus 76 ± 18 g, LVM index 30 ± 5 versus 24 ± 4 g/m(2.7) and mean wall thickness 11 ± 2 versus 9.0 ± 1 mm (all P < 0.01). Moreover, MSNA was related to LVM (r = 0.65, P < 0.002), LVM index (r = 0.46, P < 0.03) and LV mean wall thickness (r = 0.84, P < 0.001). Conclusions. In conclusion, the present study demonstrates that measures of LVM in CKD patients are greater than in healthy controls, despite a well-controlled blood pressure in the patients. Moreover, there is a positive relationship between these measures of LVM and MSNA, assessed years before, despite a standard antihypertensive treatment. These results support the notion that additional sympatholytic therapy could be beneficial.

Sympathetic hyperactivity and clinical outcome in chronic kidney disease patients during standard treatment.

BACKGROUND: Sympathetic hyperactivity has been associated with adverse clinical outcome and is common in patients with chronic kidney disease (CKD). Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) have been shown to reduce sympathetic activity in CKD patients. The present study was performed to investigate whether sympathetic hyperactivity was related to clinical outcome in CKD patients treated with ACEi or ARB. METHODS: Muscle sympathetic nerve activity (MSNA) was measured in 66 nondiabetic patients (70% men) with CKD, median age 47 years (range 21-65) and mean estimated glomerular filtration rate (eGFR) 39+/-29 ml/min per 1.73 m2. Patients were followed up for a median 78 months (range 6-123), and subsequent clinical events were recorded. RESULTS: During follow-up, average blood pressure was 131+/-11 mm Hg systolic and 83+/-6 mm Hg diastolic. Twenty-one events (4 deaths and 17 nonfatal cardiovascular events) occurred in 16 patients. MSNA among the group with events was 40+/-18 bursts/min, compared with 30+/-11 bursts/min in those with no events (p=0.009). An increase of MSNA of 10 bursts/min was related to an increased risk of an event (hazard ratio=1.6; 95% confidence interval, 1.0-2.8; p=0.08), independent of GFR and blood pressure. Age attenuated this relation. CONCLUSION: Sympathetic hyperactivity was associated with the composite of all-cause mortality and nonfatal cardiovascular events in CKD patients, despite treatment with ACEi or ARB. Further studies to investigate potential effects of additional sympatholytic therapy in these patients are warrented.

Short-term sympathetic baroreflex sensitivity increases at lower blood pressures.

OBJECTIVE: Sympathetic baroreflex sensitivity (symBRS) can be defined as the maximum sensitivity of muscle sympathetic nerve activity (MSNA) to changes in arterial blood pressure. This sensitivity is the slope of the linear middle part of the sigmoid curve that relates blood pressure to MSNA. SymBRS is known to vary with conditions, for instance during cold pressor testing. We investigated whether symBRS is affected by infusions of phenylephrine and nitroprusside. METHODS: In 10 healthy subjects, vasoactive infusions were varied in slow steps, as customary in protocols to determine 'graded infusion symBRS' (symBRS(inf)). During each step, symBRS was estimated from spontaneous beat-to-beat fluctuations (symBRS(sp)). As a secondary goal, symBRS(inf) was compared to the symBRS(sp) without infusions. RESULTS: The symBRS(sp) for MSNA burst area varied with infusions, augmenting with decreasing blood pressure, however the symBRS(sp) for burst occurrence was not affected. There were large differences between symBRS(inf) and symBRS(sp) at rest. CONCLUSIONS: symBRS(sp) varies systematically with infusions during a symBRS(inf) protocol. This denotes a fundamental difference between these methods. SIGNIFICANCE: The relationship between 'slow' infusion effects (symBRS(inf)) and changes in symBRS(sp) is elucidated. The mathematical model that describes this relationship can also explain the increase of symBRS found with other sympathoexcitatory stimuli.

Sympathetic hyperactivity in haemodialysis patients is reduced by short daily haemodialysis.

OBJECTIVE: Haemodialysis patients often have sympathetic hyperactivity. The hypothesis of this study was that a switch from three times weekly to short daily dialysis could affect sympathetic hyperactivity. METHODS: We studied 11 patients (eight men; aged 46 +/- 8 years) stable on haemodialysis for at least 1 year before and 6 months after conversion from three times to six times weekly dialysis without increasing total dialysis time (short daily dialysis). Seven patients were restudied 2 months after switching back to three times weekly haemodialysis. RESULTS: Ultrafiltration volume per session decreased from 2.4 +/- 1.0 to 1.5 +/- 0.6 l (P < 0.05). The extracellular fluid volume (bromide distribution space) did not change. Mean arterial pressure (without medication) decreased from 113 +/- 11 to 98 +/- 9 mmHg (P < 0.05). Cardiac output (Doppler echocardiography) did not change, but peripheral vascular resistance decreased from 25.4 +/- 6.4 to 21.2 +/- 3.2 mmHg per min/l (P < 0.05), in conjunction with a decrease in muscle sympathetic nerve activity (MSNA) from 39 +/- 19 to 28 +/- 15 bursts/min (P < 0.05). Ambulant 24 h blood pressure decreased and the nocturnal blood pressure dip increased during short daily dialysis. The seven patients who were switched back to alternate day haemodialysis showed a return of the high MSNA and peripheral vascular resistance. CONCLUSION: The study shows that sympathetic hyperactivity in haemodialysis patients is reduced by increasing the frequency of treatment sessions. This is probably because of the decrease in number or magnitude of the fluid fluctuations.

Differential effects of renin-angiotensin-aldosterone system inhibition, sympathoinhibition and diuretic therapy on endothelial function and blood pressure in obesity-related hypertension: a double-blind, placebo-controlled cross-over trial.

OBJECTIVES: The objective of this study is to determine the effects of renin-angiotensin-aldosterone system inhibition, sympathoinhibition and diuretic therapy on endothelial function and blood pressure in obesity-related hypertension. METHODS: A randomized, four-way, double-blind, crossover study in 31 adults with previously untreated obesity-related hypertension, in which the effects of 8 weeks' inhibition of the renin-angiotensin-aldosterone system (using aliskiren 300 mg), sympathoinhibition (using moxonidine 0.4 mg), diuretic therapy (using hydrochlorothiazide 25 mg) or placebo on flow-mediated dilation and 24-h blood pressure were compared. RESULTS: The median flow-mediated dilation during placebo was 4.0% [interquartile range (IQR) 2.9-5.5%] and was increased by aliskiren [0.81%, 95% confidence interval (CI) 0.02-1.79], but not by moxonidine (0.20%, 95% CI -0.46 to 1.03) or hydrochlorothiazide (0.39%, 95%CI -0.31%-1.26%). Similarly, compared with placebo, mean 24-h blood pressure was most reduced by aliskiren (-9.8/-6.3 mmHg) and to a lesser degree by hydrochlorothiazide (-5.9/-2.6 mmHg). Moxonidine did not significantly affect blood pressure despite reduction of muscle sympathetic nerve activity. Insulin sensitivity deteriorated during hydrochlorothiazide treatment and was unaffected by aliskiren or moxonidine. Unlike aliskiren and moxonidine, hydrochlorothiazide reduced urinary 8-iso-prostaglandin F2α-VI, a marker of oxidative stress. Vascular stiffness, systemic inflammation, leptin, adiponectin and other oxidative stress markers (plasma malondialdehyde, myeloperoxidase activity and urinary 8-hydroxydeoxyguanosine) were unaffected by treatment. CONCLUSION: Renin inhibition, but not sympathoinhibition or diuretic therapy, improves endothelial function and results in larger reductions of 24-h, office, and central blood pressure in obesity-related hypertension. This adds weight to the hypothesis that inhibition of the renin-angiotensin-aldosterone system is an effective first step in the treatment of obesity-related hypertension.

Atorvastatin reduces sympathetic activity in patients with chronic kidney disease.

BACKGROUND: Hypertensive chronic kidney disease (CKD) patients often have sympathetic hyperactivity, which appears to contribute to the pathogenesis of hypertension and cardiovascular organ damage. Experimental studies and some clinical studies have shown that statin therapy can reduce central sympathetic activity. Blockade of the renin-angiotensin system (RAS), which is standard treatment for CKD, is known to lower sympathetic activity. We hypothesized that adding a statin for 6 weeks to RAS blockade would further lower sympathetic activity in hypertensive stage 2-4 CKD patients. METHODS: In 10 stable CKD patients (eight men, aged 45 ± 11 years, estimated glomerular filtration rate 56 ± 22 ml/min per 1.73 m2), who were on chronic treatment with aliskiren 300 mg, blood pressure and sympathetic activity (quantified by assessment of muscle sympathetic nerve activity, MSNA) were assessed at baseline and 6 weeks after atorvastatin 20 mg/day was added. Ten other CKD patients served as time control and were studied twice with an interval of 6 weeks without any change in medication, to quantify within participant reproducibility. RESULTS: Mean arterial blood pressure remained stable throughout the study (93 ± 5 versus 94 ± 5 mmHg). MSNA was reduced from 28 ± 8 to 20 ± 6 bursts/min (P = 0.01), while heart rate remained stable during the study. In the control CKD group, MSNA did not change: 26 ± 5 to 25 ± 6 bursts/min. Atorvastatin reduced total and low-density lipoprotein cholesterol. CONCLUSION: Atorvastatin has a further sympatholytic effect in CKD patients, who are on chronic aliskiren, which is independent of blood pressure and heart rate.

Differential effects of acute and sustained cyclosporine and tacrolimus on sympathetic nerve activity.

BACKGROUND: We studied the effect of acute and sustained cyclosporine and tacrolimus on muscle sympathetic nerve activity (MSNA) in groups of healthy male volunteers. METHODS AND RESULTS: Acute cyclosporine in normal dose (2.5 mg/kg) increased MSNA from 11 +/- 6 to 19 +/- 8 bursts/min (P < 0.05). Acute cyclosporine in high dose (10 mg/kg) increased MSNA from 13 +/- 6 to 25 +/- 4 bursts/min (P < 0.05) and increased heart rate and mean arterial pressure (heart rate from 64 +/- 8 to 74 +/- 6 b.p.m., MAP from 92 +/- 10 to 105 +/- 8 mmHg; both P < 0.05). Sustained cyclosporine (2.5 mg/kg b.i.d. for 2 weeks) suppressed MSNA from 14 +/- 6 to 8 +/- 7 bursts/min (P < 0.05). Blood pressure increased from 89 +/- 6 to 98 +/- 6 mmHg (P < 0.05). Body weight increased and plasma renin activity was suppressed. Acute tacrolimus in regular dose (0.05 mg/kg) and high dose (0.20 mg/kg) had no effect on MSNA and blood pressure. Sustained tacrolimus (0.05 mg/kg b.i.d. for 2 weeks) had no effect on blood pressure, body weight and plasma renin activity, but decreased MSNA from 14 +/- 6 to 8 +/- 5 bursts/min (P < 0.05). CONCLUSION: Sympathetic overactivity plays a role in the acute hypertensive action of cyclosporine. Cyclosporine given during 2 weeks increases blood pressure and suppresses MSNA, possibly by volume retention. Tacrolimus, in the presently applied dosages, does not cause hypertension or sympathetic overactivity. However, sustained tacrolimus also suppresses sympathetic activity, the reason of which is unclear.

Postprandial hypotension in clinical geriatric patients and healthy elderly: prevalence related to patient selection and diagnostic criteria.

The aims of this study were to find out whether Postprandial hypotension (PPH) occurs more frequently in patients admitted to a geriatric ward than in healthy elderly individuals, what the optimal interval between blood pressure measurements is in order to diagnose PPH and how often it is associated with symptoms.The result of this study indicates that PPH is present in a high number of frail elderly, but also in a few healthy older persons. Measuring blood pressure at least every 10 minutes for 60 minutes after breakfast will adequately diagnose PPH, defined as >20 mmHg systolic fall, in most patients. However with definition of PPH as >30 mmHg systolic fall, measuring blood pressure every 10 minutes will miss PPH in one of three patients. With the latter definition of PPH the presence of postprandial complaints is not associated with the existence of PPH.

The effect of intraduodenal glucose on muscle sympathetic nerve activity in healthy young and older subjects.

OBJECTIVE: The cardiovascular response to a meal is modulated by gastric distension and the interaction of nutrients, particularly carbohydrate, within the small intestine. We tested the hypothesis that the depressor effect of small intestinal glucose is greater in older than in young subjects, because the reflex increase in muscle sympathetic nerve activity (MSNA) is blunted by age. METHODS: The effects of intraduodenal glucose infusion (IDGI) on blood pressure, heart rate and MSNA were evaluated in eight healthy young subjects (4 women; mean age +/- SEM: 28.8 +/- 3.4 years), eight healthy elderly (4 women; 75.3 +/- 1.6 years) and in two patients with symptomatic postprandial hypotension (PPH), one young (21 years), and one old (90 years). RESULTS: In both young and elderly healthy subjects, IDGI decreased blood pressure (P < 0.05), but the fall in systolic blood pressure was greater in the older subjects (-17.0 +/- 4.1 vs. -6.5 +/- 1.6 mmHg, P < 0.03). MSNA increased similarly, after infusion in both young (9.0 +/- 3.4 bursts/min) and elderly (7.8 +/- 1.0 bursts/min) subjects. Baroreflex sensitivity for number of sympathetic bursts was attenuated in the elderly (P < 0.03). The increase in burst area in the young patient with PPH was attenuated (18 vs. 63% in the healthy young group). INTERPRETATION: The fall in BP induced by IDGI was greater in healthy elderly compared to healthy young subjects. The reason for this is unclear, as they have similar increases in MSNA.

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.

Function of the clavicular part of the pectoralis major muscle after transplantation of its sternocostal part.

BACKGROUND: Muscle-sparing transplantation of the sternocostal part of the pectoralis major muscle while preserving the clavicular part of the muscle may reduce donor-site morbidity, particularly in cases where dissection of the lymph nodes of the neck has been performed. The nerve supply and motor function of the clavicular part is alleged to be preserved when the sternocostal part is transposed through the deltopectoral groove. This study aims to objectify such preservation. METHODS: Muscle activity of the remaining clavicular and abdominal muscle parts was determined electromyographically, dynamometrically, and goniometrically on 17 sides in 16 patients after head and neck reconstruction. Subjective assessment was obtained by use of a structured questionnaire. RESULTS: The electromyogram proved preservation of innervation of 16 of 17 clavicular parts. The electromyogram of the abdominal part showed no signs of denervation on 10 sides and normal, full interference patterns at maximum voluntary effort in all patients. Selective functional testing of the clavicular part revealed decreased force in horizontal adduction in 11 out of 15 patients. Still, the isolated effect of the pectoralis major transposition on shoulder function could not be objectified statistically. Subjective evaluation yielded that shoulder disability was more likely to have been correlated with loss of trapezius muscle function. CONCLUSION: We conclude that the innervation of the clavicular part, indeed, is preserved by transposition of the sternocostal part through the deltopectoral groove. This supports the validity, effectiveness, and functional acceptability of our muscle-sparing technique of partial pectoralis major transplantation.

Subtle involvement of the parasympathetic nervous system in patients with irritable bowel syndrome.

This study comprises assessment of autonomic function in irritable bowel syndrome (IBS) patients, focusing on meal-related changes. In 18 IBS patients (4 males, mean age 45+/-3.0 [SEM] years) and 19 healthy volunteers (6 males, mean age 41+/-3.5 years) blood pressure, heart rate, heart rate variability and muscle sympathetic nerve activity (MSNA) were assessed before, during and after consumption of a standardized meal. In pre- and postprandial phase Valsalva maneuver, cold pressor test (CPT) and deep breathing test were carried out and Visual Analog Scale (VAS) scores for nausea, bloating and pain were obtained. In the IBS group, the meal induced significantly higher VAS scores for pain (P=0.002) and bloating (P=0.02). During food intake, the increase in blood pressure, heart rate and MSNA was equal in patients and controls, but the increase of LF/HF ratio of heart rate variability was significantly higher in the IBS group (median [quartiles] 2.29 [1.14-3.00] versus 0.77 [0.25-1.81]; P=0.03). IBS patients scored lower on pre- and postprandial RRmax/RRmin ratio during deep breathing (DB ratio, P=0.03). The increase in MSNA (burst frequency) in response to CPT tended to be higher in the IBS patients (P=0.07). We conclude that reactivity to food intake, measured as muscle sympathetic nerve activity, is normal in IBS patients. The lower DB ratio and higher LF/HF ratio during food intake in IBS patients is an indication of a reduced parasympathetic reactivity. These results suggest that reduced baseline activity as well as responsiveness of the parasympathetic system could play a role in the pathogenesis of IBS.

Enalapril and losartan reduce sympathetic hyperactivity in patients with chronic renal failure.

The aim of this study was to compare the effects on BP and sympathetic activity of chronic treatment with an angiotensin (Ang)-converting enzyme (ACE) inhibitor and an AngII receptor blocker in hypertensive patients with chronic renal failure (CRF). In ten stable hypertensive CRF patients (creatinine clearance, 46 +/- 17 ml/min per 1.73 m(2)), muscle sympathetic nerve activity (MSNA), plasma renin activity (PRA), baroreceptor sensitivity, and 24-h ambulatory BP were measured in the absence of antihypertensive drugs (except diuretics) after 6 wk of enalapril (10 mg orally) and after 6 wk of losartan (100 mg orally). The order of the three phases was randomized. Normovolemia was controlled with diuretics and confirmed with extracellular fluid volume measurements throughout the study. Both enalapril and losartan reduced MSNA (from 33 +/- 10 to 27 +/- 13 and 27 +/- 13 bursts/min, respectively; P < 0.05) and average 24-h BP (from 141 +/- 8/93 +/- 8 to 124 +/- 9/79 +/- 8 and 127 +/- 8/81 +/- 9 mmHg; P < 0.01). PRA was not different during the treatments. The change in BP and the change in MSNA during the treatments were correlated (r = 0.70 and r = 0.63, respectively; both P < 0.05). Baroreceptor sensitivity was not affected by the treatments. This is the first study to compare the effects of ACE inhibition and AngII blockade on MSNA. In hypertensive CRF patients, enalapril and losartan equally reduced BP and MSNA. Differences in modes of action of the two drugs did not result in differences in effects on MSNA, supporting the view that AngII-mediated mechanisms contribute importantly in the pathogenesis of sympathetic hyperactivity in these patients.

Sympathetic nerve activity is inappropriately increased in chronic renal disease.

The hypothesis that in hypertensive patients with renal parenchymal disease sympathetic activity is "inappropriately" elevated and that this overactivity is a feature of renal disease and not of a reduced number of nephrons per se is addressed. Fifty seven patients with renal disease (various causes, no diabetes, all on antihypertensive medication) were studied, age range 18 to 62, creatinine clearance 10 to 114 ml/min per 1.73 m(2). Antihypertensives were stopped, but diuretics were allowed, to prevent overhydration. Matched control subjects were also studied. The effect of changes in fluid status was examined in seven patients while on and after stopping diuretics and in eight control subjects while on low- and high-sodium diet. Seven kidney donors were studied before and after unilateral nephrectomy. Sympathetic activity was quantified as muscle sympathetic nerve activity (MSNA) in the peroneal nerve. Mean arterial pressure, MSNA, and plasma renin activity were higher in patients than in control subjects, respectively (115 +/- 12 and 88 +/- 11 mmHg, 31 +/- 15 and 18 +/- 10 bursts/min, and 500 [20 to 6940] and 220 [40 to 980] fmol/L per s; P < 0.01 for all items). Extracellular fluid volume (bromide distribution) did not differ. Seven patients were studied again after stopping diuretics. MSNA decreased from 34 +/- 18 to 19 +/- 18 bursts/min (P < 0.01). Eight healthy subjects were studied during low- and high-sodium diet. MSNA was 26 +/- 12 and 13 +/- 7 bursts/min (P < 0.01). The curves relating extracellular fluid volume to MSNA were parallel in the two groups but shifted to a higher level of MSNA in the patients. In the kidney donors, creatinine clearance reduced by 25%, but MSNA was identical before and after donation. It is concluded that in hypertensive patients with renal parenchymal disease, sympathetic activity is inappropriately high for the volume status and that reduction of nephron number in itself does not influence sympathetic activity.

Sympathetic activity is increased in polycystic kidney disease and is associated with hypertension.

Hypertension is common in patients with polycystic kidney disease (PKD). This study addresses the hypothesis that sympathetic activity is enhanced in hypertensive PKD patients, not only when renal function is impaired but also when renal function is still normal. Muscle sympathetic nerve activity (MSNA, peroneal nerve), plasma renin activity (PRA), heart rate, and BP were studied in PKD patients with normal and with impaired renal function and in matched controls. In hypertensive patients with normal renal function, MSNA and mean arterial pressure (MAP) were higher than in normotensive patients (23 +/- 5 versus 15 +/- 7 bursts/min; 110 +/- 10 versus 90 +/- 3 mmHg; P < 0.05), whereas PRA and heart rate did not differ. In PKD with chronic renal failure (CRF) (creatinine clearance rate, 39 +/- 19 ml/min), MAP, MSNA and PRA were higher than in controls (resp, 116 +/- 7 versus 89 +/- 9 mmHg; 34 +/- 14 versus 19 +/- 9 bursts/min; 405 [20 to 1640] versus 120 [40 to 730] fmol/L per sec; all P < 0.05). Heart rate in PKD CRF did not differ from controls. MSNA correlated with MAP (r = 0.42; P = 0.01) and age with MSNA (r = 0.45; P < 0.01). Regression line of age and MSNA in patients was steeper than that in controls. This study indicates that MSNA is increased in hypertensive PKD patients regardless of renal function. The data support the idea that sympathetic hyperactivity contributes to the pathogenesis of hypertension in PKD.

Subtle involvement of the sympathetic nervous system in amyotrophic lateral sclerosis.

The literature on the involvement of the autonomic nervous system (ANS) in amyotrophic lateral sclerosis (ALS) is conflicting. We therefore investigated several aspects of autonomic function, namely muscle sympathetic nerve activity (MSNA), blood pressure, cardiac function (electrocardiogram; ECG), and respiration in 16 patients with sporadic ALS and in 12 age-matched healthy volunteers, both at rest and during sympathoexcitatory stimulation. We measured MSNA by provoking venous pooling during short-lasting lower body negative pressure (LBNP) and during the cold pressor test (CPT). To assess the vagal (baroreflex) control of heart rate (HR), we measured spontaneous baroreflex sensitivity (BRS). To assess the involvement of the ANS beyond the cardiovascular system, we measured the sympathetic skin response (SSR). The stand-up test showed that none of the subjects had orthostatic intolerance. In comparison with the control group, the ALS patients had an increased HR and a decreased BRS at rest, and a reduced MSNA response to LBNP. The CPT response was normal and the total MSNA at rest did not differ significantly from that of controls. The latencies of the palmar and plantar SSR were prolonged, and in 3 ALS patients there was no plantar SSR. The results indicate that the sympathetic nervous system shows subtle abnormalities in ALS, predominantly sympathetic overactivity. They also point to the involvement of the preganglionic sympathetic column as the cause of the higher sympathetic activity and the absence of SSR. The higher sympathetic activity is postulated to be due to changes in modulation of the sympathetic system, whereas the absence of the SSR is probably caused by disruption of the reflex pathway.