Biochemical Quantification of Sympathetic Nervous Activity in Humans Using Radiotracer Methodology

Esler, M.; Leonard, P; O’Dea, Kerin; Jackman, Graham P.; Jennings, Garry; Korner, Paul I.

doi:10.1097/00005344-198200041-00030

Cited by 34 publications

(12 citation statements)

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“…Cardiac and total body sympathetic activity was estimated using radiotracer methodology (19). For these measurements, tritiated NE (New England Nuclear, Boston, MA) was infused into a peripheral vein to steady-state concentration in plasma.…”

Section: Methodsmentioning

confidence: 99%

Cardiac sympathetic activation in patients with pulmonary arterial hypertension

Mak

Witte

Al‐Hesayen

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Patients with congestive heart failure (CHF) due to left ventricular (LV) dysfunction have sympathetic activation specifically directed to the myocardium. Although pulmonary arterial hypertension (PAH) is associated with increased systemic sympathetic activity, its impact on sympathetic drive to ventricular myocardium is unknown. Fifteen patients with PAH (9 women; 54 Ϯ 12 years) were studied: 10 with idiopathic PAH and 5 with a connective tissue disorder. We measured hemodynamics, as well as radiolabeled and endogenous concentrations of arterial and coronary sinus norepinephrine (NE). These measures were repeated after inhaled nitric oxide (NO). Measurement of transcardiac NE concentrations and the cardiac extraction of radiolabeled NE allowed calculation of the corrected transcardiac gradient of NE (CTCG of NE). Comparative data were collected from 15 patients (9 women: 55 Ϯ 12 yr) with normal LV function and 15 patients with CHF (10 women; 53 Ϯ 12 yr). PAH patients had elevated arterial NE concentrations compared with those with normal LV function but were similar to those with CHF. The CTCG of NE was higher in those with PAH than in the normal LV group (3.6 Ϯ 2.2 vs. 1.5 Ϯ 0.9 pmol/ml; P Ͻ 0.01) but similar to that seen in those with CHF (3.3 Ϯ 1.4; P ϭ NS). Inhaled NO, which reduced pulmonary artery pressure and increased cardiac output, had no effect on cardiac sympathetic activity. Therefore, cardiac sympathetic activation occurs in PAH. The mechanism of this activation remains uncertain but does not involve elevations in left heart filling pressure. pulmonary hypertension; norepinephrine; hemodynamics PULMONARY HYPERTENSION IS defined as a mean pulmonary artery pressure of more than 25 mmHg at rest and is classified into five groups based upon etiology (42, 43). Idiopathic pulmonary arterial hypertension (IPAH) and other forms of pulmonary hypertension due to abnormalities in the pulmonary vasculature [pulmonary arterial hypertension (PAH)] require the exclusion of other causes, particularly abnormalities of left heart function.

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Section: Methodsmentioning

confidence: 99%

Cardiac sympathetic activation in patients with pulmonary arterial hypertension

Mak

Witte

Al‐Hesayen

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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“…= b: ;t a * ---, IL NA to plasma and the plasma clearance of NA, and drugs may affect plasma NA levels by modifying either of these determinants. Radiotracer methods have previously been used to demonstrate that the reduction in plasma NA levels after clonidine is solely due to reduced release and spillover into plasma of NA, and not increased clearance of NA from plasma (Esler et al, 1982).…”

Section: Catecholamines In Plasmamentioning

confidence: 99%

Sedative and cardiovascular effects of medetomidine, a novel selective alpha 2‐adrenoceptor agonist, in healthy volunteers.

Scheinin

Kallio

Koulu

et al. 1987

Brit J Clinical Pharma

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1 Single intravenous doses (25, 50 and 100 ,ug) of medetomidine an imidazole derivative), a selective a2-adrenoceptor agonist, were administered to eight healthy male volunteers in a double-blind, placebo-controlled study. 2 The following dose-related effects, all of which were compatible with an agonistic action of the drug at a2-adrenoceptors, were noted: reductions of systolic and diastolic blood pressure (maximum 18/11 mm Hg), heart rate (maximum 10 beats min-'), saliva secretion (maximum 84%) and noradrenaline levels in plasma (maximum 70%). 3 Dose-dependent sedation or impairment of vigilance was also observed, both by subjective and objective (critical flicker fusion threshold) assessments, with the highest dose actually inducing sleep in five of the subjects. 4 The observed effects were in general agreement with those previously seen after intravenous administration of the centrally acting antihypertensive a2-adrenoceptor activating drug, clonidine, but of a shorter duration. 5 The relative importance of a2-adrenoceptors located in peripheral tissues and in the central nervous system for the drug's cardiovascular effects could not be determined, but the high lipid solubility of the compound and the rapid onset of sedation are in favour of a major central component. 6 Medetomidine may be a useful tool for the investigation of the physiology and pharmacology of a2-adrenoceptors in man. In addition, the therapeutic and diagnostic uses of the compound should be investigated in pathological conditions related to increased sympathetic neuronal activity.

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“…Measurements of NE spillover allow for repeated assessment of sympathetic activity in conscious, undisturbed animals. The purpose of this study was to investigate total body NE kinetics in a rat model of chronic ANG II-salt hypertension, as an index of global sympathetic outflow.Since Esler and colleagues (16) first applied radioisotope dilution principles for measurements of NE release and clearance in humans, it has become clear that these methods provide a more accurate assessment of sympathetic transmitter release than allowed by measurements of plasma catecholamines alone (13,19,57). The major advantage of whole body NE spillover as an index of global sympathetic outflow is that the dynamic processes of NE clearance and NE spillover can be distinguished when analyzing plasma NE levels (14).…”

mentioning

confidence: 99%

“…Since Esler and colleagues (16) first applied radioisotope dilution principles for measurements of NE release and clearance in humans, it has become clear that these methods provide a more accurate assessment of sympathetic transmitter release than allowed by measurements of plasma catecholamines alone (13,19,57). The major advantage of whole body NE spillover as an index of global sympathetic outflow is that the dynamic processes of NE clearance and NE spillover can be distinguished when analyzing plasma NE levels (14).…”

mentioning

confidence: 99%

Whole body norepinephrine kinetics in ANG II-salt hypertension in the rat

King¹,

Novotný²,

Swain³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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The purpose of this study was to investigate total body norepinephrine (NE) kinetics as an index of global sympathetic nervous system (SNS) outflow in a rat model of chronic ANG II-salt hypertension. Male Sprague-Dawley rats fed a 0.4% (normal salt, NS) or 2% (HS) NaCl diet were instrumented with arterial and venous catheters. After 5 days of recovery and a 3-day control period, ANG II (150 ng.kg(-1).min(-1)) was given subcutaneously by minipump for 14 days. Plasma NE levels and total body NE spillover and clearance were determined on control day 3 and ANG II infusion days 7 and 14 using radioisotope dilution principles. To perform this analysis, 3H-NE and NE were measured in arterial plasma after a 90-min infusion of tracer amounts of 3H-NE. Mean arterial pressure (MAP) was similar during the control period in NS and HS rats; however, MAP increased to a higher level in HS rats. During the control period, plasma NE tended to be lower in rats on HS, whereas NE clearance tended to be higher in HS rats. As a result NE spillover was similar in NS and HS rats during the control period. In NS rats, plasma NE, NE spillover, and NE clearance were unchanged by ANG II. In contrast, in rats on the HS diet, plasma NE and NE spillover increased during ANG II infusion, whereas NE clearance was unchanged. In conclusion, a HS diet alone or ANG II infusion in animals fed NS do not affect global sympathetic outflow. However, the additional hypertensive response to ANG II in animals fed HS is accompanied by SNS activation.

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Biochemical Quantification of Sympathetic Nervous Activity in Humans Using Radiotracer Methodology

Cited by 34 publications

References 0 publications

Cardiac sympathetic activation in patients with pulmonary arterial hypertension

Cardiac sympathetic activation in patients with pulmonary arterial hypertension

Sedative and cardiovascular effects of medetomidine, a novel selective alpha 2‐adrenoceptor agonist, in healthy volunteers.

Whole body norepinephrine kinetics in ANG II-salt hypertension in the rat

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