Sympathetic Activation in Obese Normotensive Subjects

Abstract

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.

Influence of Sibutramine on blood pressure: evidence from placebo-controlled trials

“…In a large subgroup of obese patients, sympathetic activity is increased even at rest. 15,28 Our analysis has several limitations. The analysis was retrospective.…”

“…12 The complex interaction of peripheral and central nervous mechanisms makes it difficult to predict the cardiovascular response to sibutramine in patients with altered sympathetic activity, such as obese hypertensives. 15 A recent post marketing surveillance study suggested a significant decrease in blood pressure with sibutramine in obese hypertensives. 16 We pooled data from two recent clinical trials to determine the effect of sibutramine treatment on blood pressure in obese subjects with different degrees of hypertension.…”

Mechanisms of obesity-induced hypertension

“…Microneurograhic techniques, a direct method of measuring increased SNS activity, provide evidence of high muscle SNS activity in obese subjects. 4 High-caloric intake increases norepinephrine turnover in peripheral tissues, raises resting plasma norepinephrine concentrations-an indirect measurement of SNS activity-and amplifies the rise of plasma norepineprhine in response to stimuli such as upright posture. 5 High dietary content in fat and carbohydrate has been suggested to acutely stimulate peripheral a 1 -and b-adrenergic receptors, leading to elevated sympathetic activity and hypertension.…”

“…A reduced sensitivity of the arterial baroreflex manifested as a diminished response in heart rate to BP changes may occur in long-standing hypertension and obesity, 4 presumably because of various mechanisms, including a concomitant increase in central sympathetic outflow and the effects of arteriosclerotic lesions leading to an increased stiffness of the large arteries in which the receptors are located. We have earlier reported an increased carotid arteries intima media thickness in obese subjects independently of the BP levels, even in a normotensive BP range, suggesting an early course of the atherosclerotic process in obesity.…”

“…There is also evidence that SNS response to hypoxia may affect the renal circulation in patients with obstructive sleep apnea, an abnormality often seen in the obese population. 4,30 Hyperfiltration as a result of heightened blood flow to the kidney is always present in obesity, long before glomerulopathy occurs. It is, therefore, the primary cause of gradual sclerosis of the glomeruli wall because of physical stress and eventually of a vicious circle in which nephrons are injured, sodium retention worsens and arterial pressure reaches higher values to maintain sodium balance.…”