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

Short versus long-term effects of different dihydropyridines on sympathetic and baroreflex function in hypertension

Antihypertensive treatment with dihydropyridines may be accompanied by sympathetic activation. Data on whether this is common to all compounds and similar in the various phases of treatment are not univocal, however. In 28 untreated essential hypertensives (age, 56.4\ub11.8 years; mean \ub1SEM) finger blood pressure (BP, Finapres), heart rate (HR, ECG), plasma norepinephrine (NE, high-performance liquid chromatography), and muscle sympathetic nerve traffic (MSNA, microneurography) were measured at rest and during baroreceptor manipulation (vasoactive drugs) in the placebo run-in period and after randomization to double-blind acute and chronic (8 weeks) felodipine (10 mg/d, n = 14) or lercanidipine (10 mg/d, n = 14). Acute administration of both drugs induced pronounced BP reductions and marked increases in HR, NE, and MSNA. After 8 weeks of treatment, BP reductions were similar to those observed after acute administration, whereas HR, NE, and MSNA responses were markedly attenuated (-7%, -32%, and -14%, respectively; P<0.05). There was a small residual increase in sympathetic activity in the felodipine group, whereas in the lercanidipine group, all adrenergic markers returned to baseline values. Baroreflex control of HR and MSNA was markedly impaired (-42% and -48%, respectively) after acute drug administration, with a recovery and complete resetting during chronic treatment. Thus, the sympathoexcitation induced by 2 different dihydropyridines is largely limited to the acute administration. The 2 drugs have, nevertheless, a different chronic sympathetic effect, indicating that dihydropyridines do not homogeneously affect this function. The acute sympathoexcitation, but not the small between-drugs differential chronic adrenergic effect, is accounted for by baroreflex impairment

Comparison between reproducibility and sensitivity of muscle sympathetic nerve traffic and plasma noradrenaline in man

1. Although plasma noradrenaline and muscle sympathetic nerve traffic have been shown to be suitable markers of sympathetic activity in man, no study has systematically compared the reproducibility and sensitivity of these two indices of adrenergic tone. 2. Reproducibility data were collected in 10 subjects, in whom plasma noradrenaline was assessed by HPLC on blood samples withdrawn from an antecubital vein and efferent postganglionic muscle sympathetic nerve activity was measured by microneurography from a peroneal nerve, together with arterial blood pressure (Finapres technique). Measurements were obtained in a first session (session 1), 60 min later (session 2) and after 14 days (session 3). While muscle sympathetic nerve activity values recorded in the three different experimental sessions were closely and significantly correlated with each other (r always > 0.90, P < 0.001), noradrenaline showed a less significant correlation between sessions 1 and 2 (r = 0.71, P < 0.05) or no correlation between sessions 1 and 3 (r = 0.45, P not significant). 3. Sensitivity data were collected by evaluating muscle sympathetic nerve activity and noradrenaline values in three different age groups (young, middle-age and old subjects, n = 18), in three groups with different blood pressures (normotensive, mild and severe hypertensive subjects, n = 30) and in a group of eight subjects before and after a physical training programme, i.e. conditions known to increase or reduce sympathetic cardiovascular drive. Muscle sympathetic nerve activity was significantly increased by aging and hypertension, and reduced by physical training. The noradrenaline changes were much less marked and consistent. 4. These data suggest that muscle sympathetic nerve activity has a greater short- and medium-term reproducibility than noradrenaline. In several conditions known to modify sympathetic cardiovascular drive muscle sympathetic nerve activity also appears to change more clearly than noradrenaline

Sympathetic nerve traffic and asymmetric dimethylarginine in chronic kidney disease.

BACKGROUND AND OBJECTIVES: Sympathetic overactivity and high levels of the endogenous inhibitor of NO synthase asymmetric dimethylarginine (ADMA) are prevalent risk factors in chronic kidney disease (CKD). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: 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. RESULTS: 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. CONCLUSIONS: Sympathetic activity and ADMA may share a pathway leading to renal disease progression, proteinuria, and LV concentric remodeling in CKD patients

Effect of detraining on the cardiopulmonary reflex in professional runners and hammer throwers

In professional athletes with marked cardiac hypertrophy, reflex influences originating from cardiopulmonary receptors are impaired. To determine whether the reflex is restored after termination of physical training and regression of cardiac hypertrophy 8 former athletes (age 31 +/- 6 years, mean +/- SD) who stopped agonistic activity for 5 +/- 1 years were compared with 15 sedentary subjects (27 +/- 7 years) and 19 active professional athletes (22 +/- 7 years). Cardiopulmonary receptor stimulation and deactivation were obtained by increasing and reducing left ventricular end-diastolic diameter (echocardiography) through leg raising and nonhypotensive lower body negative pressure, respectively. Left ventricular mass index (echocardiography) was markedly and significantly (p less than 0.01) greater in athletes (135 +/- 6 g/m2) than in former athletes (105 +/- 4 g/m2) whose value was similar to that of sedentary subjects (98 +/- 4 g/m2). The reduction in forearm vascular resistance and plasma norepinephrine induced by increasing left ventricular end-diastolic diameter was 24 and 23% less in athletes than in former athletes whose responses were similar to those of sedentary subjects. This was the case also for the responses induced by reducing left ventricular end-diastolic diameter. In contrast, the hemodynamic responses to cold pressor test were similar in the 3 groups. It is concluded that the impairment of the cardiopulmonary reflex observed in athletes is largely reversible when physical training is terminated. This may be due to regression of left ventricular hypertrophy

Effects of ageing on the cardiopulmonary receptor reflex in normotensive humans

This study examined the effects of ageing on the cardiopulmonary receptor regulation of vasomotor tone in skeletal muscle and renin release by the kidney. To this end, the changes in forearm vascular resistance (mean arterial pressure divided by plethysmographically measured forearm blood flow), plasma noradrenaline concentration and plasma renin activity were measured in eight young (23 +/- 2 years, mean +/- s.e.m.) and seven elderly healthy subjects (69 +/- 2 years) during manoeuvres which altered cardiopulmonary receptor activity. The cardiopulmonary receptors were stimulated by increasing central venous pressure through passive leg-raising and deactivated by reducing central venous pressure through non-hypotensive (-15 mmHg) and hypotensive (-40 mmHg) levels of lower body negative pressure. During either manoeuvre, central venous pressure changed by the same amount in both groups, but the reflex changes in forearm vascular resistance, plasma noradrenaline and plasma renin activity were significantly less in elderly subjects. Since the increase in forearm vascular resistance induced by a cold pressor test was comparable in young and elderly subjects, a non-specific depression of cardiovascular responsiveness to neural stimuli can be excluded. Thus, healthy normotensive elderly subjects show an impairment of both vascular and neurohumoral influences exerted by cardiopulmonary receptors. This may be involved in the decreased ability of the elderly to cope with gravity challenges

Decreased cardiopulmonary reflexes with aging in normotensive humans

Arterial baroreflex is impaired in the normotensive elderly. However, no information is available on the effects of aging on another major reflex mechanism of cardiovascular control, i.e., cardiopulmonary reflex. Three groups of normotensive subjects divided according to age were evaluated during leg raising, which increased central venous pressure, and during lower body negative pressures, which reduced central venous pressure without altering blood pressure and heart rate. These maneuvers stimulated and deactivated cardiopulmonary receptors with only little involvement of arterial baroreceptors. During lower body negative pressures, central venous pressure decreased similarly in three groups, but reflex increases in forearm vascular resistance, plasma norepinephrine, and plasma renin activity were smaller in elderly than in middle-aged and young subjects. Furthermore, during leg raising, comparable increases in central venous pressure caused reflex vascular and humoral responses that were smaller in elderly than in middle-aged and young subjects. Elderly subjects had smaller changes in left ventricular diameter in response to changes in central venous pressure. Blood pressure and vascular responses to cold pressor test were similar in the three groups, excluding a hyporeactivity of older subjects to neural stimuli. Thus aging is associated with an impairment of the cardiopulmonary reflex. This may originate from an impaired ability of cardiac receptors to sense alterations in central blood volume because of an age-dependent reduction in cardiac compliance

Cardiopulmonary receptor reflexes in normotensive athletes with cardiac hypertrophy

Cardiopulmonary receptor control of the circulation is impaired in a variety of diseases having cardiac hypertrophy as a common feature. Whether this also occurs in the so-called "physiological" cardiac hypertrophy of the athlete, however, is unknown. We studied nine sedentary healthy subjects and 19 age-matched professional runners or hammer throwers who had trained at least 2 hours per day, 5 days per week for 7 years. The left ventricular mass index (echocardiography) was 99 +/- 7.4 and 135 +/- 5.9 g/m2 in the two groups, respectively. Cardiopulmonary receptor stimulation and deactivation were obtained by increasing and reducing left ventricular end-diastolic diameter for 5 minutes by leg raising and lower body negative pressure, keeping both stimuli at a level not affecting blood pressure and heart rate. In the sedentary healthy subjects, forearm vascular resistance (the ratio between mean arterial pressure and forearm blood flow) and plasma norepinephrine fell during leg raising (forearm vascular resistance, -7 +/- 1.7 units; norepinephrine, -57.4 +/- 1.4 pg/ml) and increased during lower, body negative pressure (forearm vascular resistance, 20 +/- 5.3 units; norepinephrine, 97.7 +/- 21.5 pg/ml). For similar or greater alterations in left ventricular end-diastolic diameter, the correspondent changes observed in the professional runners or hammer throwers were -5.3 +/- 1.3 units (forearm vascular resistance), -35.4 +/- 9.6 pg/ml (norepinephrine), 9.1 +/- 1.4 units (forearm vascular resistance), and 30.9 +/- 6.9 pg/ml (norepinephrine). This represented an attenuation of 25%, 38%, 55%, and 68%, respectively (p less than 0.01), of the control response.(ABSTRACT TRUNCATED AT 250 WORDS