Sympathetic Overactivation in Patients With Essential Hypertension and Hepatic Iron Overload

Iron overload has been recently shown to be associated with a hyperadrenergic state in genetic hemochromatosis. Whether this is also the case in essential hypertension, characterized by sympathetic activation and frequently by body iron overload, is unknown. In 17 healthy normotensive controls (age 52.3±3.2 years, mean±SE), in 21 age-matched patients with hypertension with iron overload (HT+), defined by serum ferritin levels, and in 28 hypertensives without this condition, we measured efferent postganglionic muscle sympathetic nerve traffic (microneurography), heart rate and blood pressure variability (power spectral analysis), serum ferritin, and metabolic variables. Muscle sympathetic nerve traffic was significantly ( P <0.02 at least) greater in HT+ than in patients with hypertension without iron overload and normotensive subjects both when expressed as bursts incidence over time (41.8±1.4 versus 31.5±1.4 and 23.6±0.9 bursts/min) and as bursts corrected for heart rate (55.3±1.8 versus 42.3±1.2 and 31.7±1.2 bursts/100 heartbeats). In HT+, low-frequency systolic blood pressure variability was significantly reduced. In HT+, but not in the other 2 groups, muscle sympathetic nerve traffic was significantly related to serum ferritin ( r =0.51, P <0.03), transferrin saturation ( r =0.47, P <0.03), and hepatic iron load ( r =0.76, P <0.0001, magnetic resonance imaging), as well as to homeostatic model assessment index values ( r =0.46, P <0.05). These data provide the first evidence that in HT+ elevated serum ferritin is associated with a hyperadrenergic state of greater magnitude than the one seen in patients with hypertension without iron overload. They also show that the potentiation of the sympathetic activation detected in HT+ is related to elevated serum ferritin and to the associated metabolic alterations, possibly participating in the increased cardiovascular risk characterizing iron overload.

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The role of carotid chemoreceptors in the sympathetic activation by adenosine in humans

Clinical Science ◽

10.1042/cs20030174 ◽

2004 ◽

Vol 106 (1) ◽

pp. 75-82 ◽

Cited By ~ 8

Author(s):

Henri J. L. M. TIMMERS ◽

Gerard A. RONGEN ◽

John M. KAREMAKER ◽

Wouter WIELING ◽

Henri A. M. MARRES ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Sodium Nitroprusside ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Adenosine Infusion ◽

Sympathetic Activation ◽

Nerve Activity ◽

Induced Hypotension ◽

Carotid Chemoreceptors

The direct vasodilatory and negative chronotropic effects of adenosine in humans are counterbalanced by a reflex increase in sympathetic nerve traffic. A suggested mechanism for this reflex includes peripheral chemoreceptor activation. We, therefore, assessed the contribution of carotid chemoreceptors to sympatho-excitation by adenosine. Muscle sympathetic nerve activity was recorded during adenosine infusion (140 µg·kg-1·min-1 for 5 min) in five patients lacking carotid chemoreceptors after bilateral carotid body tumour resection (one male and four female, mean age 51±11 years) and in six healthy controls (two male and four female, mean age 50±7 years). Sympathetic responses to sodium nitroprusside injections were assessed to measure baroreceptor-mediated sympathetic activation. In response to adenosine, controls showed no change in blood pressure, an increase in heart rate (+48.2±13.2%; P<0.003) and an increase in sympathetic nerve activity (+195±103%; P<0.022). In contrast, patients showed a decrease in blood pressure (-14.6±4.9/-17.6±6.0%; P<0.05), an increase in heart rate (+25.3±8.4%; P<0.032) and no significant change in sympathetic activity. Adenosine-induced hypotension in individual patients elicited less sympathetic activation than equihypotensive sodium nitroprusside injections. In humans lacking carotid chemoreceptors, adenosine infusion elicits hypotension due to the absence of significant sympatho-excitation. Chemoreceptor activation is essential for counterbalancing the direct vasodilation by adenosine. In addition, blunting of the baroreflex sympathetic response to adenosine-induced hypotension may indicate a direct sympatho-inhibitory effect of adenosine.

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Sympathetic and reflex abnormalities in heart failure secondary to ischaemic or idiopathic dilated cardiomyopathy

Clinical Science ◽

10.1042/cs1010141 ◽

2001 ◽

Vol 101 (2) ◽

pp. 141-146 ◽

Cited By ~ 30

Author(s):

Guido GRASSI ◽

Gino SERAVALLE ◽

Giovanni BERTINIERI ◽

Carlo TURRI ◽

Maria Luisa STELLA ◽

...

Keyword(s):

Heart Failure ◽

Blood Pressure ◽

Heart Rate ◽

Dilated Cardiomyopathy ◽

Sympathetic Nerve ◽

Left Ventricular ◽

Clinical Severity ◽

Idiopathic Dilated Cardiomyopathy ◽

Left Ventricular Ejection ◽

Sympathetic Activation

Congestive heart failure (CHF) is characterized by a sympathetic activation and a baroreflex impairment whose degree is directly related to the clinical severity of the disease. However, whether these abnormalities vary according to the ischaemic or idiopathic dilated nature of the CHF state has not been conclusively documented. In patients with a clinically stable, chronic CHF state in New York Heart Association functional class II and III, due either to ischaemic heart disease (IHD; n = 22, age 60.3±2.4 years, means±S.E.M.) or to idiopathic dilated cardiomyopathy (IDC; n = 20, age 58.9±2.8 years), and in 30 age-matched controls, we measured arterial blood pressure (using a Finapres device), heart rate (by electrocardiogram) and postganglionic muscle sympathetic nerve traffic (by microneurography) at rest and during baroreceptor manipulation induced by the vasoactive drug-infusion technique. Blood pressure values were not significantly different in CHF patients and controls. Compared with controls, heart rate was similarly increased and left ventricular ejection fraction (by echocardiography) similarly reduced in CHF patients with IHD or IDC. Muscle sympathetic nerve traffic was significantly greater in CHF patients than in controls, and did not differ between patients with IHD or IDC (67.3±4.2 and 67.8±3.8 bursts/100 heart beats respectively). This was also the case for the degree of baroreflex impairment. These data show that CHF states due to IHD or to IDC are characterized by a similar degree of peripheral sympathetic activation and by a similar impairment of the baroreflex function. Thus the neuroadrenergic and reflex abnormalities characterizing CHF are independent of its aetiology.

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