Determination of norepinephrine apparent release rate and clearance in humans

Esler, Murray; Jackman, Graham P.; Bobik, Alex; Kelleher, Dianne; Jennings, Garry; Leonard, P; Skews, Helen; Korner, Paul I.

doi:10.1016/0024-3205(79)90371-0

Cited by 338 publications

(182 citation statements)

References 16 publications

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“…Plasma noradrenaline (NA) and adrenaline concentrations were determined by HPLC with electrochemical detection (Hallman et al 1978). Total body NA clearance and spillover to plasma were measured with the technique of Esler et al (1979) as follows: Leg clearance was calculated as: LPF w NA ex . Since NA clearance and spillover at 10, 15 and 20 min of the infusion period were similar, the mean of these three measurements was taken as the representative value.…”

Section: Blood Haemoglobin Concentration ([Hb]) and O 2 Saturation (Sj)mentioning

confidence: 99%

Chronic hypoxia increases blood pressure and noradrenaline spillover in healthy humans

Calbet¹

2003

J Physiology

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Section: Blood Haemoglobin Concentration ([Hb]) and O 2 Saturation (Sj)mentioning

confidence: 99%

Chronic hypoxia increases blood pressure and noradrenaline spillover in healthy humans

Calbet¹

2003

J Physiology

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“…Total body NE spillover was measured by the radiotracer method 17 and calculated according to the following formula:…”

Section: Calculationsmentioning

confidence: 99%

Differentiated Response of the Sympathetic Nervous System to Angiotensin-Converting Enzyme Inhibition in Hypertension

et al. 2000

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Abstract-Hypertension with renal artery stenosis is associated with both an activated renin-angiotensin system and elevated sympathetic activity. Therefore, in this condition it may be favorable to use a therapeutic modality that does not reflexly increase heart rate, renin secretion, and sympathetic nervous activity. The purpose of the present study was to assess overall, renal, and muscle sympathetic activity after short-term administration of an angiotensin-converting enzyme inhibitor (enalaprilat) and a nonspecific vasodilator (dihydralazine) to hypertensive patients with renal artery stenosis. Forty-eight patients undergoing a clinical investigation for renovascular hypertension were included in the study. An isotope dilution technique for assessing norepinephrine spillover was used to estimate overall and bilateral renal sympathetic nerve activity. In 11 patients simultaneous intraneural recordings of efferent muscle sympathetic nerve activity were performed. Thirty minutes after dihydralazine administration, mean arterial pressure fell by 15%, whereas plasma angiotensin II, muscle sympathetic nerve activity, heart rate, and total body norepinephrine spillover increased (PϽ0.05 for all). In contrast, after enalaprilat administration a fall in arterial pressure similar to that for dihydralazine was followed by decreased angiotensin II levels and unchanged muscle sympathetic nerve activity, heart rate, and total body norepinephrine spillover, whereas renal norepinephrine spillover increased by 44% (PϽ0.05). Acute blood pressure reduction by an angiotensin-converting enzyme inhibitor provokes a differentiated sympathetic response in patients with hypertension and renal artery stenosis, inasmuch that overall and muscle sympathetic reflex activation are blunted, whereas the reflex renal sympathetic response to blood pressure reduction is preserved. (Hypertension. 2000;36:543-548.)Key Words: hypertension, renovascular Ⅲ sympathetic nervous system Ⅲ renin-angiotensin system R enovascular hypertension is a condition associated with both an activated renin-angiotensin system and elevated sympathetic nerve activity. 1,2 Previous data, obtained in experimental models, indicate a positive interaction between the renin-angiotensin and the sympathetic nervous systems. 3 Therefore, in renovascular hypertension it may be favorable to use a therapeutic modality that does not reflexly further increase heart rate, renin secretion, and sympathetic nervous activity. It is well known that certain drugs used in cardiovascular medicine affect various indices of sympathetic activity. For example, sympathetic activity increases in response to nonspecific vasodilators, whereas therapy with angiotensin-converting enzyme (ACE) inhibitors has demonstrated reduced peroneal sympathetic activity. 4 Thus, it appears that vasodilators and ACE inhibitors produce different sympathetic nerve responses; the effects of the latter could be due to either a direct-acting central mechanism 5,6 or a reduction of angiotensin II (Ang II) facilitatory e...

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“…After separation by refrigerated centrifugation, the plasma was stored at -80 Њ C. Plasma catechol levels were assayed using liquid chromatography with electrochemical detection (Eisenhofer et al 1986 (Esler et al 1979). Neuronal uptake (Eisenhofer et al 1991) and NE stores at the active release sites (Eisenhofer et al 1991;Eisenhofer et al 1996) were assessed from the 3 H-DHPG and 3 H-NE concentrations.…”

Section: Biochemical Variablesmentioning

confidence: 99%

“…The rate of release of endogenous NE into arterial plasma and the rate of clearance from plasma was determined with the following equations: 1) CL ϭ IR/[ 3 H]-NE and 2) SP ϭ CLxNEa; where CL is the arterial plasma NE clearance (ml/min), IR is the infusion rate of [ 3 H]-NE, [ 3 H]-NE is the arterial plasma concentration of [ 3 H]-NE, SP is the NE spillover rate (pmol/min) into arterial plasma, and NEa is the arterial plasma concentration of endogenous NE (Esler et al 1979). Neuronal uptake (Eisenhofer et al 1991) and NE stores at the active release sites (Eisenhofer et al 1991;Eisenhofer et al 1996) were assessed from the 3 H-DHPG and 3 H-NE concentrations.…”

Section: Biochemical Variablesmentioning

confidence: 99%

Effects of Risperidone on the Peripheral Noradrenegic System in Patients with Schizophrenia A Comparison with Clozapine and Placebo

Elman

Goldstein

Green

et al. 2002

Neuropsychopharmacology

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Risperidone is an atypical antipsychotic drug that increases plasma norepinephrine (NE) levels, but the mechanism behind this effect is unclear. We measured arterial plasma levels of NE and other catechols during intravenous infusion of tritium-labeled NE ( 3 H-NE) in risperidone-Clozapine is an atypical antipsychotic drug (APD) with efficacy superior to that of conventional agents and with little or no extrapyramidal signs or symptoms (EPS) (Kane et al. 1988;Lieberman et al. 1989;Breier et al. 1994a;Meltzer 1995;Meltzer et al. 1996). Because these advantageous therapeutic properties are accompanied by unusually severe side effects, scientists have been searching for clozapine-like APDs that would share its beneficial features but not induce bone marrow toxicity, seizures, or hypotension. This search has resulted in the introduction of four "newer atypical APDs" (i.e., risperidone, olanzapine, quetiapine, and ziprasidone), all of which have important effects on both dopaminergic and serotonergic neurotransmitter systems. Because none of these compounds has been proven as efficacious as the prototype, clozapine, in the treatment of resistant cases, continued research is focusing on other neurotransmitter systems affected by clozapine.Clozapine profoundly increases norepinephrine (NE) levels in both CSF (Ackenheil 1989;Lieberman et al. 1989;Lieberman et al. 1991;Pickar et al. 1992) and plasma (Pickar et al. 1992;Green et al. 1993;Davidson et al. 1993;Breier 1994;Breier et al. 1994b;Schulz et al. 1996;Schulz et al. 1997;Brown et al. 1997;Fleischhaker et al. 1998;Elman et al. 1999), an effect not seen with typical APDs. In some (Breier et al. 1994b;Schulz et al. 1997;Fleischhaker et al. 1998), but not all (Brown et al. 1997) studies, plasma NE increases have been related to clinical improvement, suggesting that this pharmacological effect may play a role in clozapine's beneficial central actions. In this context, findings implicating noradrenergic dysregulation in the pathophysiology of schizophrenia (Stein and Wise 1971;Sternberg 1984;Breier et al. 1990;Rao and Moller 1994;Breier 1994;Yamamoto et al. 1994;Litman et al. 1996;Breier et al. 1998;Goff and Evins 1998;Friedman et al. 1999a;Friedman et al. 1999b;Klimek et al. 1999) further support inquiry into the relevance of noradrenergic mechanisms in the action of APDs.We have reported previous data suggesting that high plasma NE levels in clozapine-treated patients result from increases in the appearance rate of the endogenously released NE in the plasma (spillover) rather than from decreased neuronal uptake of NE, inhibition of intraneuronal monoamine oxidase (MAO), or adrenoceptor antagonism . Risperidone, the next atypical antipsychotic drug marketed in the United States after clozapine, is associated with a low incidence of EPS and may have improved efficacy compared with conventional agents (Kane and McGlashan 1995;Pickar 1995;Campbell et al. 1999). Interestingly, risperidone has also recently been observed in a clinical study to produce a modest (i.e., 58%) inc...

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Determination of norepinephrine apparent release rate and clearance in humans

Cited by 338 publications

References 16 publications

Chronic hypoxia increases blood pressure and noradrenaline spillover in healthy humans

Chronic hypoxia increases blood pressure and noradrenaline spillover in healthy humans

Differentiated Response of the Sympathetic Nervous System to Angiotensin-Converting Enzyme Inhibition in Hypertension

Effects of Risperidone on the Peripheral Noradrenegic System in Patients with Schizophrenia A Comparison with Clozapine and Placebo

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