Mechanisms responsible for sympathetic activation by cigarette smoking in humans

Background The presser and tachycardic effects of cigarette smoking are associated with an increase in plasma catecholamines, suggesting the dependence of these effects on adrenergic stimulation. Whether the stimulation occurs at a central or a peripheral level and whether reflex mechanisms are involved is unknown. Methods and Results In nine normotensive healthy subjects (age, 33.0+/-3.5 years, mean+/-SEM), we measured blood pressure (Finapres device), heart rate (ECG), calf blood how and vascular resistance (venous occlusion plethysmography), plasma norepinephrine and epinephrine (high-performance liquid chromatography assay), and postganglionic muscle sympathetic nerve activity (microneurography from the peroneal nerve) while subjects were smoking,a filter cigarette (nicotine content, 1.1 mg) or were in control condition. Cigarette smoking (which raised plasma nicotine measured by highperformance liquid chromatography from 1.0+/-0.9 to 44.2+/-7.1 ng/mL) markedly and significantly increased mean arterial pressure (+13.2+/-2.3%), heart rate (+30.3+/-4.7%), calf vascular resistance (+12.1+/-4.9%), plasma norepinephrine (+34.8+/-7.0%), and plasma epinephrine (+90.5+/-39.0%). In contrast, muscle sympathetic nerve activity showed a marked reduction (integrated activity -31.8+/-5.1%, P<.01). The reduction was inversely related to the increase in mean arterial pressure (r=-.67, P<.05), but the slope of the relation was markedly less (-54.1+/-7.5%, P<.05) than that obtained by intravenous infusion of phenylephrine in absence of smoking. The hemodynamic and neurohumoral changes were still visible 30 minutes after smoking and occurred again on smoking a second cigarette. Sham smoking was devoid of any hemodynamic and neurohumoral effect. Conclusions These data support the hypothesis that in humans the sympathetic activation induced by smoking depends on an increased release and/or a reduced clearance of catecholamines at the neuroeffector junctions. Central sympathetic activity is inhibited by smoking, presumably via a baroreceptor stimulation triggered by the smoking-related presser response. The baroreflex is impaired by smoking, however, indicating that partial inability to reflexly counteract the effect of sympathetic activation is also responsible for the presser response

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

Mechanisms responsible for sympathetic activation by cigarette smoking in humans

Background The presser and tachycardic effects of cigarette smoking are associated with an increase in plasma catecholamines, suggesting the dependence of these effects on adrenergic stimulation. Whether the stimulation occurs at a central or a peripheral level and whether reflex mechanisms are involved is unknown. Methods and Results In nine normotensive healthy subjects (age, 33.0+/-3.5 years, mean+/-SEM), we measured blood pressure (Finapres device), heart rate (ECG), calf blood how and vascular resistance (venous occlusion plethysmography), plasma norepinephrine and epinephrine (high-performance liquid chromatography assay), and postganglionic muscle sympathetic nerve activity (microneurography from the peroneal nerve) while subjects were smoking,a filter cigarette (nicotine content, 1.1 mg) or were in control condition. Cigarette smoking (which raised plasma nicotine measured by highperformance liquid chromatography from 1.0+/-0.9 to 44.2+/-7.1 ng/mL) markedly and significantly increased mean arterial pressure (+13.2+/-2.3%), heart rate (+30.3+/-4.7%), calf vascular resistance (+12.1+/-4.9%), plasma norepinephrine (+34.8+/-7.0%), and plasma epinephrine (+90.5+/-39.0%). In contrast, muscle sympathetic nerve activity showed a marked reduction (integrated activity -31.8+/-5.1%, P<.01). The reduction was inversely related to the increase in mean arterial pressure (r=-.67, P<.05), but the slope of the relation was markedly less (-54.1+/-7.5%, P<.05) than that obtained by intravenous infusion of phenylephrine in absence of smoking. The hemodynamic and neurohumoral changes were still visible 30 minutes after smoking and occurred again on smoking a second cigarette. Sham smoking was devoid of any hemodynamic and neurohumoral effect. Conclusions These data support the hypothesis that in humans the sympathetic activation induced by smoking depends on an increased release and/or a reduced clearance of catecholamines at the neuroeffector junctions. Central sympathetic activity is inhibited by smoking, presumably via a baroreceptor stimulation triggered by the smoking-related presser response. The baroreflex is impaired by smoking, however, indicating that partial inability to reflexly counteract the effect of sympathetic activation is also responsible for the presser response

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

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

Sympathomoderating influence of benazepril in essential hypertension

In essential hypertension, captopril attenuates forearm vasoconstriction reflexly induced by deactivation of cardiopulmonary and arterial baroreceptors, thus exerting a sympathomoderating effect. We investigated whether this is a common effect of angiotensin converting enzyme (ACE) inhibitors

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

Sympathetic activation in obese normotensive subjects

Human obesity is characterized by profound alterations in the hemodynamic and metabolic states. Whether these alterations involve sympathetic drive is controversial. In 10 young obese subjects (body mass index, 40.5 +/- 1.2 kg/m2, mean +/- SEM) with normal blood pressure and 8 age-matched lean normotensive control subjects, we measured beat-to-beat arterial blood pressure (Finapres technique), heart rate (electrocardiogram), postganglionic muscle sympathetic nerve activity (microneurography at the peroneal nerve), and venous plasma norepinephrine (high-performance liquid chromatography). The measurements were performed in baseline conditions and, with the exception of plasma norepinephrine, during baroreceptor stimulation and deactivation caused by increases and reductions of blood pressure via intravenous infusions of phenylephrine and nitroprusside. Baseline blood pressure and heart rate were similar in obese and control subjects. Plasma norepinephrine was also similar in the two groups. Muscle sympathetic nerve activity, however, was 38.6 +/- 5.1 bursts per minute in obese subjects and less than half that level in control subjects (18.7 +/- 1.3 bursts per minute), the difference being highly statistically significant (P < .02). Muscle sympathetic nerve activity and heart rate were reduced during phenylephrine infusion and increased during nitroprusside infusion, but the changes were about half as great in obese subjects as in control subjects. Thus, even in the absence of any blood pressure alteration, human obesity is characterized by a marked sympathetic activation, possibly because of an impairment of reflex sympathetic restraint. This may be involved in the high rate of hypertension and cardiovascular complications seen in obesity

Sympathetic activation in obese normotensive subjects

Human obesity is characterized by profound alterations in the hemodynamic and metabolic states. Whether these alterations involve sympathetic drive is controversial. In 10 young obese subjects (body mass index, 40.5 +/- 1.2 kg/m2, mean +/- SEM) with normal blood pressure and 8 age-matched lean normotensive control subjects, we measured beat-to-beat arterial blood pressure (Finapres technique), heart rate (electrocardiogram), postganglionic muscle sympathetic nerve activity (microneurography at the peroneal nerve), and venous plasma norepinephrine (high-performance liquid chromatography). The measurements were performed in baseline conditions and, with the exception of plasma norepinephrine, during baroreceptor stimulation and deactivation caused by increases and reductions of blood pressure via intravenous infusions of phenylephrine and nitroprusside. Baseline blood pressure and heart rate were similar in obese and control subjects. Plasma norepinephrine was also similar in the two groups. Muscle sympathetic nerve activity, however, was 38.6 +/- 5.1 bursts per minute in obese subjects and less than half that level in control subjects (18.7 +/- 1.3 bursts per minute), the difference being highly statistically significant (P < .02). Muscle sympathetic nerve activity and heart rate were reduced during phenylephrine infusion and increased during nitroprusside infusion, but the changes were about half as great in obese subjects as in control subjects. Thus, even in the absence of any blood pressure alteration, human obesity is characterized by a marked sympathetic activation, possibly because of an impairment of reflex sympathetic restraint. This may be involved in the high rate of hypertension and cardiovascular complications seen in obesity