Increased sympathetic activity contributes to hypertension in patients with chronic renal disease. ACE inhibition controls hypertension and decreases sympathetic hyperactivity.

Abstract. 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 lowand 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 Ϯ 12 and 88 Ϯ 11 mmHg, 31 Ϯ 15 and 18 Ϯ 10 bursts/min, and 500 [20 to 6940] and 220 [40 to 980] fmol/L per s; P Ͻ 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 Ϯ 18 to 19 Ϯ 18 bursts/min (P Ͻ 0.01). Eight healthy subjects were studied during low-and high-sodium diet. MSNA was 26 Ϯ 12 and 13 Ϯ 7 bursts/min (P Ͻ 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.

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Abstract. 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 Ϯ 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 Ϯ 10 to 27 Ϯ 13 and 27 Ϯ 13 bursts/min, respectively; P Ͻ 0.05) and average 24-h BP (from 141 Ϯ 8/93 Ϯ 8 to 124 Ϯ 9/79 Ϯ 8 and 127 Ϯ 8/81 Ϯ 9 mmHg; P Ͻ 0.01). PRA was not different during the treatments. The change in BP and the change in MSNA during the treatments were correlated (r ϭ 0.70 and r ϭ 0.63, respectively; both P Ͻ 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 hyperactivity in chronic renal failure (CRF) is caused by mechanisms arising in the failing kidneys (1). The renin system is often activated in hypertensive patients with CRF. There is clear evidence that high circulating angiotensin II (AngII) levels can stimulate central sympathetic outflow by a direct effect on the vasomotor center in the brain stem, which in humans can be quantified as increased muscle sympathetic nerve activity (MSNA) (2). We showed that MSNA is increased in patients with CRF and that this hyperactivity was reduced by chronic angiotensin-converting enzyme (ACE) inhibition (3). These findings support the idea that AngII is involved in the pathogenesis of the sympathetic hyperactivity. However, ACE inhibition did not completely normalize the MSNA in these patients. There is increasing evidence that sympathetic hyperactivity contributes to the cardiovascular risk profile, not only by its effect on BP, but also independent of this effect (4).The hypothesis in the present study was that AngII receptor blockade in an equally effective antihypertensive regimen more effectively reduces the sympathetic hyperactivity than ACE inhibition. AngII receptor blockers are well accepted as antihypertensive agents in patients with CRF (5-7). Their BP lowering effect is comparable to that of ACE inhibitors (7,8). However, although both classes of drugs primarily interf...

The effect of high dose intravenous immunoglobulin (IVIg) treatment was studied in six patients with multifocal motor neuropathy (MMN

Abstract-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 54Ϯ31 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 Ն6 weeks of enalapril (10 mg PO), losartan (100 mg PO), or eprosartan (600 mg PO Key Words: sympathetic hyperactivity Ⅲ muscle sympathetic nerve activity Ⅲ renal hypertension Ⅲ chronic kidney disease Ⅲ ACE inhibition Ⅲ angiotensin II receptor blocker A ngiotensin-converting enzyme inhibition (ACEi) and angiotensin II (Ang II) receptor blockade (ARB) are well accepted as the cornerstones of the treatment of chronic kidney disease (CKD) patients, because they may help to prevent kidney failure progression. CKD is often characterized by the presence of sympathetic hyperactivity. This may be important because of its effect on cardiovascular function and structure. [1][2][3][4] We have shown previously that these agents reduce sympathetic hyperactivity. [5][6][7] Because sympathetic hyperactivity might affect clinical outcome, it seems important to know its prevalence and to what extent it is normalized by ACEi and ARB. Therefore, the aims of the present study were, first, to assess the prevalence of sympathetic hyperactivity by quantifying muscle sympathetic nerve activity (MSNA) in a sizable group of hypertensive CKD patients in comparison with control subjects and to establish factors that predict sympathetic activity and, second, to assess the efficacy of ACEi and ARB to normalize sympathetic activity.

Stretching the stomach wall in young healthy subjects causes an increase in muscle sympathetic nerve activity and in blood pressure, the gastrovascular reflex. We compared healthy elderly subjects with healthy young subjects to find out whether the gastrovascular reflex attenuates in normal ageing and we studied whether there was a difference in autonomic function or gastric compliance that could explain this possible attenuation. Muscle sympathetic nerve activity, finger blood pressure and heart rate were continuously recorded during stepwise isobaric gastric distension using a barostat in eight healthy young (6 men and 2 women, 27 ± 3.2 years, mean ± s.e.m.) and eight healthy elderly subjects (7 men and 1 woman, 76 ± 1.5 years). Changes in cardiac output and total peripheral arterial resistance were calculated from the blood pressure signal. The baseline mean arterial pressure and muscle sympathetic nerve activity were higher in the elderly group (both P < 0.05) and muscle sympathetic nerve activity increase during the cold pressor test was lower in the elderly group (P = 0.005). During stepwise gastric distension, the elderly subjects showed an attenuated increase in muscle sympathetic nerve activity compared to the young subjects (P < 0.01). The older group tended to show a higher increase in mean arterial pressure (P = 0.08), heart rate (P = 0.06) and total peripheral arterial resistance (P = 0.09) The cardiac output rose slightly in both groups without significant difference between groups. The fundic compliance did not differ between groups. We conclude that stepwise gastric distension caused an increase in muscle sympathetic nerve activity in both groups, but the increase in the elderly was attenuated.

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.