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Results for “Norepinephrine”

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PubMed2000

Effect of acute treatment with YM992 on extracellular norepinephrine levels in the rat frontal cortex.

The effects of acute treatment with (S)-2-[[(7-fluoroindan-4-yl)oxy]methyl]morpholine monohydrochloride (YM992), venlafaxine, fluoxetine and citalopram on extracellular norepinephrine levels were examined in the rat frontal cortex by in vivo microdialysis. YM992 (3, 10, 30 mg/kg, i.p.) dose-dependently increased extracellular norepinephrine levels (3-fold at 10 mg/kg, 5. 5-fold at 30 mg/kg). While venlafaxine and 30 mg/kg fluoxetine also produced significant increases in norepinephrine levels, 30 mg/kg citalopram had no effect. The combined administration of MDL100,907 (a selective 5-HT(2A) receptor antagonist) and citalopram did significantly increase norepinephrine levels compared with either saline or citalopram treatment. Therefore, a synergistic effect due to 5-HT reuptake inhibition and 5-HT(2A) receptor antagonism of YM992 may partly contribute to the increase of extracellular norepinephrine levels. YM992 enhances the neurotransmission of not only 5-HT system but also norepinephrine, and as such may have a preclinical profile different from that of a selective serotonin reuptake inhibitor.

Analysis of Variance↗

PubMed1996

Intrategmental infusion of cocaine decreases dopamine release and enhances norepinephrine release in the medial prefrontal cortex.

We evaluated the effects of local cocaine infusion into the A10 (ventral tegmental area), the cell body of the mesocorticolimbic dopaminergic pathway, on the extracellular concentrations of dopamine and norepinephrine in the medial prefrontal cortex, one of its terminal fields. A 1-ml Hamilton syringe was used to infuse a cocaine solution, either 20 or 200 microM, into the ventral tegmental area of anesthetized rats for 120 min through a microdialysis probe. The pure artificial cerebrospinal fluid (0 microM cocaine) infusion served as a control and a lidocaine (100 microM) infusion was administered to prevent the local anesthetic effect of cocaine. After intrategmental cocaine infusion (either 20 or 200 microM), extracellular dopamine and norepinephrine in the ventral tegmental area both increased significantly to a steady state level (208 +/- 42 and 148 +/- 23% for low dose and 220 +/- 24 and 150 +/- 15% for high dose). Simultaneously, the 200-microM cocaine infusion caused a significant decrease in extracellular dopamine (77 +/- 5%) but an increase in norepinephrine (140 +/- 6%) in the medial prefrontal cortex. The local anesthetic, lidocaine, produced no effects on the dopamine or norepinephrine output (neither in the ventral tegmental area nor in the medial prefrontal cortex). This study not only supports recent findings of an increase in extracellular dopamine and norepinephrine in the ventral tegmental area on intrategmental cocaine infusion, but also demonstrates that cocaine infused locally in the ventral tegmental area can decrease dopamine and increase norepinephrine at a remote terminal area (medial prefrontal cortex). Finally, the introduction rate of cocaine into the ventral tegmental area by retrograde microdialysis was found to be 0.83 ng/min for the low dose and 8.14 ng/min for the high dose.

Anesthetics, Local↗

PubMed1998

Effects of endothelin-1 on norepinephrine-induced vasoconstriction in deoxycorticosterone acetate-salt hypertensive rats.

We investigated the effects of endothelin-1 on pressor responses to norepinephrine in perfused mesenteric arteries of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The response to norepinephrine (10(-6) M) was significantly increased in DOCA-salt rats compared with that in uninephrectomized control rats. Perfusion of the arteries with subpressor dose of endothelin-1 (3 x 10(-10) M) for 15 min markedly enhanced the pressor responses to norepinephrine (10(-6) and 3 x 10(-6) M) in control rats and this effect was significantly prevented by BQ788 [N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D -1-methoxycarbonyl-tryptophanyl-D-norleucine] (10(-6) M), but not by FR139317 ((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl]amino-4-+ ++methylpentanoyl]amino-3-[3-(1-methyl-1H-indoyl)]propionyl]ami no-3-(2-pyridyl)propionic acid) (10(-6) M). In DOCA-salt hypertensive rats, increased pressor response to norepinephrine was declined to the level of control rats by BQ788, but not by FR139317. In contrast to the case seen with control rat, exogenous endothelin-1 had little effect on pressor responses to norepinephrine in the arteries of DOCA-salt hypertensive rats. Total immunoreactive endothelin content in the arteries of DOCA-salt hypertensive rats was significantly higher than that of uninephrectomized control rats. These results suggest that endothelin-1 enhances contractile responses to norepinephrine through endothelin ETB receptor. Moreover, this phenomenon is stimulated tonically by endogenous endothelin-1 in DOCA-salt hypertensive rats and may contribute to the maintenance of hypertension in DOCA-salt rats.

Animals↗

PubMed1996

Thiocyanate induces vasoconstriction in rat-tail artery primed with norepinephrine.

The vasoregulating effects of thiocyanate (SCN-) were studied by means of a new rat tail artery perfusion model that uses constant driving pressure (1000 mm H2O). When a 30 mm long artery was perfused with 20 micromol/L verapamil, the flow rate increased 6%. Norepinephrine (10 to 1000 nmol/L) caused a dose-dependent flow inhibition. SCN- alone (0.05 to 5 mmol/L) had a slight, if any, effect on the arterial flow. However, when the artery was pretreated with norepinephrine (1000 nmol/L) for 10 minutes, followed by a basal-medium washout that left a 13% norepinephrine-induced flow inhibition, 0.05 to 5 mmol/L SCN- caused a marked flow rate reduction of between 20.4% +/- 9.8% and 28.0% +/- 21.8%, as calculated for the entire test perfusion. The decrease in flow rate correlated with the SCN- concentration (p < 0.05) and showed a clear reversibility. A similar SCN(-)-induced (0.05 mmol/L) vasoconstriction (p < 0.05) was seen when the artery was given a basal tone by continuous perfusion with low-dose norepinephrine, 10 nmol/L. Nifedipine (100 nmol/L) abolished the effect of 0.05 mmol/L SCN- but did not affect the norepinephrine priming. We conclude that SCN- amplifies the norepinephrine-induced vascular smooth muscle tone and that this may be caused by an altered calcium channel activity.

Animals↗

PubMed2001

The effects of norepinephrine and prostaglandin E1 on pharmacokinetics of lidocaine in isolated perfused rat liver.

We hypothesized that depression of liver function by norepinephrine can be improved by prostaglandin E1. Isolated perfused rat liver was selected as an experimental model, since the flow rate can be regulated in it. Twenty-one rats were randomly allocated to three groups: control, norepinephrine, and norepinephrine and prostaglandin E1 groups. The liver was perfused in a recirculating system at a constant flow rate of 20 ml/min. After administration of two milligrams of lidocaine in each group, lidocaine and monoethylglycinexylidide concentrations in the recirculating system were measured. Lidocaine pharmacokinetics were analyzed using the SAAM II program, including metabolic rate from lidocaine to monoethylglycinexylidide using time-concentration curves. Norepinephrine significantly increased perfusion pressure and the area under the time-concentration curve for lidocaine. Norepinephrine decreased the clearance and the elimination rate constant of lidocaine compared with those in the control group. Although administration of prostaglandin E1 after infusion of norepinephrine did not significantly change perfusion pressure, it significantly (p < 0.05) improved metabolic rate, clearance and the elimination rate constant of lidocaine in the isolated rat liver model.

Alprostadil↗

PubMed2003

Interactions of norepinephrine and galanin in the central amygdala and lateral bed nucleus of the stria terminalis modulate the behavioral response to acute stress.

Many aspects of drug abuse and addiction share neurobiological substrates with the modulatory processes underlying the response and adaptation to acute stress. In particular, the ascending noradrenergic system has been implicated in facilitating the response to stress, and in stress-induced reinstatement of drug seeking behavior. Thus, to better understand the link between stress and addictive behaviors, it would be informative to understand better the modulatory function of the ascending noradrenergic system, and its interaction with other neurotransmitters with which it is closely associated or co-localized, such as the neuropeptide galanin. In this paper, we review a series of studies investigating the functional interactions of norepinephrine and galanin in modulating the behavioral response to acute stress in two components of the extended amygdala, the central nucleus of the amygdala and the lateral bed nucleus of the stria terminalis. We showed that norepinephrine facilitates behavioral reactivity to stress on the elevated plus-maze and social interaction tests. However, when stress-induced activation of the noradrenergic system was enhanced by blocking inhibitory adrenergic autoreceptors, galanin release was recruited in the central amygdala, acting to attenuate the behavioral response to stress. By contrast, stress-induced galanin release in the lateral bed nucleus appeared to be independent of enhanced noradrenergic activation, and unlike the central amygdala, both galanin and norepinephrine facilitated behavioral stress reactivity in the bed nucleus. The different modes of interaction and differential region- and response-specificity of galanin and norepinephrine suggest that a complex neural circuit interconnecting these two regions is involved in the modulatory effects of norepinephrine and galanin on the behavioral response to stress. Such complexity may allow for flexibility and plasticity in stress adaptation, and may also contribute to behavioral changes induced by chronic drug administration. Thus, the interaction of galanin and norepinephrine may be a viable target for the future development of novel therapeutic strategies for treating behavioral disorders related to stress or drug abuse.

Acute Disease↗

PubMed2001

Norepinephrine acts via alpha(2) adrenergic receptors to suppress N-type calcium channels in dissociated rat median preoptic nucleus neurons.

The median preoptic (MnPO) nucleus, a key CNS site for hydromineral and cardiovascular homeostasis, receives a dense norepinephrine innervation from brainstem autonomic centers. Since norepinephrine is known to influence neuronal excitability by modulating calcium channel function, we applied whole cell patch clamp techniques to study calcium currents in 116 dissociated MnPO neurons, including 30 cells identified by a retrograde label as projecting to the hypothalamic paraventricular nucleus. Norepinephrine (3-50 microM) suppressed high-voltage-activated calcium currents (HVA I(Ca)) in 80% of cells, selectively blockable by yohimbine and mimicked by UK14,304 and clonidine. The norepinephrine effect was relieved by strong prior depolarization, indicating a voltage-dependent component. Intracellular GTP-gamma-S blocked the effect. Blockade by extracellular NEM suggested involvement of pertussis-toxin sensitive G-proteins. Based on pharmacological properties, these HVA I(Ca)s had the following composition: 40-45% N-type (blockable by omega-conotoxin GVIA); 20-25% L-type (blockable by nimodipine); 15-20% P/Q-type (blockable by omega-agatoxin IVA). Since approximately 75% of the norepinephrine effect was blockable with omega-conotoxin GVIA, we conclude that postsynaptic alpha(2) adrenoceptors preferentially suppress N-type calcium channels, revealing a novel mechanism whereby norepinephrine can modulate excitability in MnPO neurons.

Adrenergic alpha-Agonists↗

PubMed1999

Elevated urinary norepinephrine in interstitial cystitis.

OBJECTIVES: To measure urinary catecholamines and determine the extent to which they may be elevated in urine from patients with interstitial cystitis (IC). METHODS: Random urine samples from patients with IC (n = 111) and urine from normal volunteers (n = 92) were acidified on collection (voided and catheterized specimens) and assayed for catecholamine (norepinephrine or normetanephrine) by enzyme-linked immunosorbent assay. Creatinine levels in these urine samples were also measured. RESULTS: Analysis of the data indicated that patients with IC had a higher urinary level of the neurotransmitter norepinephrine compared with the measured levels in the urine of normal volunteers (89.1 +/- 58.3 versus 54.9 +/- 37.1 microg/g creatinine, P <0.05). The metabolite normetanephrine was similar in the urine samples from these two groups. Urine from patients with bladder outlet obstruction (n = 11) did not have elevated amounts of urinary norepinephrine. The norepinephrine levels were not statistically different in the urine samples from patients with symptomatic and asymptomatic IC. The elevated urinary levels in patients with IC did not decrease after treatment with sodium pentosanpolysulfate (Elmiron), heparinoids, dimethyl sulfoxide, or combinations of these during 1 to 15 months of treatment. CONCLUSIONS: Norepinephrine was found to be elevated in the urine from patients with IC compared with urine from normal controls. This would be consistent with increased sympathetic (adrenergic) activity from the bladders of patients with IC or possibly from increased adrenal activity, since stress is associated with symptom increase in some patients with IC. Norepinephrine levels did not decrease with treatment nor did they differ between symptomatic and asymptomatic patients at the time of urine collection.

Adult↗

PubMed2001

Intravenous cocaine increases plasma epinephrine and norepinephrine in humans.

Cocaine has been shown to activate the sympathoadrenal system in both animal and human studies. Controlled human studies have found inconclusive results regarding whether acute cocaine treatment elevates plasma epinephrine and norepinephrine concentrations. The purpose of this study was to investigate whether commonly abused doses of cocaine increase plasma epinephrine and norepinephrine concentrations in humans, in a double-blind, placebo-controlled study. Five male cocaine users were given an intravenous injection of 0.46 mg/kg dose of cocaine or placebo, on two consecutive days. Plasma epinephrine and norepinephrine concentrations were significantly increased in response to cocaine injection compared to placebo. Peak plasma epinephrine and norepinephrine concentrations were reached 3 and 12 min after cocaine injection, respectively. While changes in epinephrine levels following cocaine were correlated with systolic blood pressure and heart rate changes, changes in plasma norepinephrine were correlated with diastolic blood pressure and heart rate changes following cocaine administration. These results suggest that plasma epinephrine and norepinephrine can be used as a measure for cocaine induced sympathoadrenal system activation.

Adult↗

PubMed1991

Effects of phosphatase inhibitors and a protein phosphatase on norepinephrine secretion by permeabilized bovine chromaffin cells.

A protein phosphatase and phosphatase inhibitors were used to examine the role of protein phosphorylation in the regulation of norepinephrine secretion in digitonin-permeabilized bovine chromaffin cells. Addition of okadaic acid, a potent inhibitor of type 1 and type 2A protein phosphatases, or 1-naphthylphosphate, a more general phosphatase inhibitor, to digitonin-permeabilized chromaffin cells caused about a 100% increase in the amount of norepinephrine secreted in the absence of Ca2+ (in 5 mM EGTA) without affecting the amount of norepinephrine secreted in the presence of 10 microM free Ca2+. This stimulation of norepinephrine secretion by protein phosphatase inhibitors suggests that in the absence of Ca2+ there is a slow rate phosphorylation and that this phosphorylation triggers secretion. Addition of an exogenous type 2A protein phosphatase caused almost a 50% decrease in Ca(2+)-dependent norepinephrine secretion. Thus, the amounts of norepinephrine released both in the absence of Ca2+ and in the presence of Ca2+ appear to depend upon the level of protein phosphorylation.

Adrenal Medulla↗

PubMed1990

Effects of epinephrine and norepinephrine on cerebral oxygen delivery and consumption during open-chest CPR.

The effect of epinephrine and norepinephrine on cerebral oxygen delivery and consumption after five minutes of cardiopulmonary arrest and three minutes of open-chest cardiac massage was studied in 21 pigs. Norepinephrine, like epinephrine, has a marked alpha- and beta 1-sympathomimetic activity, but compared with epinephrine, the degree of beta 2-stimulation is weak. Epinephrine probably stimulates cerebral oxygen and glucose consumption by its beta 2-adrenergic effect. After three minutes of CPR, three groups of seven animals each blindly received either placebo (control group), 45 micrograms/kg epinephrine, or 45 micrograms/kg norepinephrine. During CPR but before drug administration, cerebral blood flow was 23 +/- 14 mL/min/100 g in the control group, 30 +/- 7 mL/min/100 g in the epinephrine group, and 30 +/- 11 mL/min/100 g in the norepinephrine group. At 90 seconds after epinephrine, cerebral blood flow increased to 54 +/- 14 mL/min/100 g and after norepinephrine, to 58 +/- 22 mL/min/100 g (P less than .05). Cerebral perfusion pressure for both drugs was significantly higher than the control group. Compared with mechanical measures alone, cerebral oxygen delivery rose from 4.3 +/- 1.2 to 7.4 +/- 1.7 mL/min/100 g after epinephrine and from 3.7 +/- 1.4 to 7.3 +/- 2.7 mL/min/100 g after norepinephrine (P less than .05). There was no increase in cerebral oxygen consumption after both catecholamines, and cerebral oxygen extraction ratio decreased. Cerebral glucose delivery increased in relation to glucose consumption, and extraction ratio did not change significantly after both catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Norepinephrine in cochlear microcirculation of guinea pigs.

The blood flow in the radiating arteriole through a small cochlear fenestra was recorded with motion pictures in anesthetized guinea pigs, before and after norepinephrine injection into the ipsilateral carotid artery. The flow velocity was determined by measuring the displacement of plasma space running through the radiating arteriole per second. Norepinephrine injection of 0.01 and 0.15 mg/kg increased both flow velocity and arterial blood pressure. The flow velocity increase related directly to the increase in arterial blood pressure. However, a larger norepinephrine dose (1.2 and 2.5 mg/kg) led to transient cessation in flow, which was independent of the blood pressure increase. Dilatation of vessel diameter was always observed with the rise in blood pressure, irrespective of norepinephrine doses. When blood flow in the radiating arteriole stopped after a large norepinephrine injection, the arteriole's vascular lumen was completely obstructed by the aggregated red blood cells. These results suggested that cochlear microcirculation is disturbed by microemboli formed by norepinephrine-induced platelet hyperaggregation.

Animals↗

PubMed1997

Increased concentrations of plasma epinephrine and norepinephrine in patients with eclampsia.

We measured plasma catecholamine concentrations on admission (after eclamptic fit) and after 6 days of delivery in 21 eclamptic patients and on admission in 15 normotensive pregnant women in Bangladesh. Plasma epinephrine and norepinephrine concentrations in eclamptic patients were significantly higher on admission than those of normotensive pregnant women (P < 0.0001). Plasma catecholamine concentrations and mean arterial blood pressure had return to be almost normal as normotensive pregnant women after 6 days of delivery, resulting in no correlation between mean arterial blood pressure and plasma catecholamines. On admission (after eclamptic fit) mean arterial blood pressure was positively correlated with plasma epinephrine (r = 0.626, P < 0.002) and norepinephrine (r = 0.553, P < 0.008) concentrations in patients with eclampsia. The amount of proteinuria was also significantly correlated with plasma epinephrine (r = 0.515, P < 0.02) and norepinephrine (r = 0.606, P < 0.003) concentrations. Number of convulsions was significantly correlated with concentrations of plasma epinephrine (r = 0.514, P < 0.02), norepinephrine (r = 0.521, P < 0.01) and mean arterial blood pressure (r = 0.535, P < 0.01). A positive correlation was found between time passed after convulsion with plasma epinephrine (r = 0.515, P < 0.02) and norepinephrine (r = 0.570, P < 0.006) concentrations. These suggested that the increased plasma levels of epinephrine and norepinephrine in eclamptic patients were well correlated with the severity of the clinical features of eclampsia.

Bangladesh↗

PubMed1998

Desensitization and resensitization of norepinephrine release in the rat hippocampus with repeated nicotine administration.

Desensitization of norepinephrine release was investigated with repeated intravenous (i.v.) infusions of nicotine and in vivo microdialysis of the hippocampus. At 100 min intervals, rats received three infusions of one of the following doses of nicotine: 0.045, 0.09 or 0.135 mg/kg. Doses of 0.09 mg/kg or higher increased norepinephrine release (F= 2.41, P < 0.05). However, the norepinephrine response to the second or third infusion was significantly reduced, compared to the first. The extent of desensitization and rate of resensitization was investigated further by administering consecutive infusions of nicotine (0.135 mg/kg) 40, 60, 100 or 200 min apart. Less norepinephrine was released after a second nicotine infusion given 40 to 100 min later, but this was not reduced further by a third infusion. Norepinephrine release was unchanged with a 200 min inter-infusion interval. Therefore, in the hippocampus, maximal desensitization of nicotine-stimulated norepinephrine release occurs as early as 40 min and persists for at least 100 min; thereafter, resensitization becomes the dominant process.

Animals↗

PubMed1997

Beta-endorphin inhibition of endogenous norepinephrine release from the A2 noradrenergic nucleus in vitro: role of mu opiate receptors and Na+ ion permeability.

An in vitro approach was used to determine the opioid receptor subtype mediating beta-endorphin inhibition of endogenous norepinephrine release from the A2 nucleus in the caudal dorsomedial medulla of rats. The voltage-sensitive Na+ channel blocker tetrodotoxin was used to investigate the role of Na+-dependent action potentials in beta-endorphin inhibition of K+-evoked norepinephrine release. Human beta-endorphin(1-31) inhibited K+-evoked norepinephrine release in a concentration-dependent fashion. Activation of delta- and kappa-opioid receptors had no effect on endogenous norepinephrine release. The inhibitory effect of beta-endorphin was blocked in a concentration-dependent manner by the mu-opioid receptor antagonist CTOP (Cys2, Tyr3, Orn5, Pen7 amide). Tetrodotoxin (TTX) inhibited norepinephrine release evoked by 25 mM K+ in a concentration-dependent manner and blocked the inhibitory effects of beta-endorphin. These results indicate that beta-endorphin acts on mu-opioid receptors to inhibit K+-evoked norepinephrine release from A2 neurons and suggest that the receptors involved are not located on noradrenergic nerve terminals.

Adrenergic Fibers↗

PubMed2001

Ambulatory norepinephrine treatment of severe autonomic orthostatic hypotension.

OBJECTIVES: This study was designed to establish a patient-controlled, ambulatory norepinephrine treatment of refractory orthostatic hypotension due to primary autonomic failure. BACKGROUND: Autonomic dysfunction leads to disabling postural hypotension. Particularly in primary autonomic dysfunction, repeated syncope and immobilization can be the result. Medical treatment of orthostatic hypotension often fails in advanced cases. METHODS: Ambulatory, patient-controlled norepinephrine therapy was initiated in six patients with orthostatic hypotension due to primary autonomic failure that had been refractory to conventional treatment. Before this therapy, three patients were bedridden; one was immobilized in a wheelchair. All had recurrent syncope and tolerated upright tilt-table testing for less than 15 min despite extensive medical treatment. For ambulatory treatment, a port-a-cath system was implanted and, using a CADD ambulatory infusion pump, norepinephrine was infused in individually adjusted dosages. RESULTS: Norepinephrine infusion therapy enabled all patients to sit, stay and walk around for more than 45 min. One patient died after a five-year treatment period, another after nine months because of nonhemorrhagic brain stem infarctions, both in the absence of norepinephrine treatment. The remaining four patients are still mobile after a period of 19, 10, 9 and 7 months, respectively. None of them has suffered complications due to arterial hypo- or hypertension, and there has been no infection of the infusion system. CONCLUSIONS: In these selected patients with refractory orthostatic hypotension due to primary autonomic dysfunction, ambulatory norepinephrine infusion therapy has proved to be a promising new therapeutic option. Further long-term studies including more patients are necessary to assess additional indications, reliability and safety of this new method.

Aged↗

PubMed2002

Conservation of the cardiostimulant effects of (-)-norepinephrine across Ser49Gly and Gly389Arg beta(1)-adrenergic receptor polymorphisms in human right atrium in vitro.

OBJECTIVE: The goal of this study was to determine whether the cardiostimulant effects of the endogenous beta(1)-adrenergic receptor (AR) agonist, (-)-norepinephrine are modified by polymorphic (Serine49Glycine [Ser49Gly], Glycine389Arginine [Gly389Arg]) variants of beta(1)-ARs in the nonfailing adult human heart. BACKGROUND: Human heart beta(1)-ARs perform a crucial role in mediating the cardiostimulant effects of (-)-norepinephrine. An understanding of the significance of Ser49Gly and Gly389Arg polymorphisms in the human heart is beginning to emerge, but not as yet in adult patients who have coronary artery disease (CAD). METHODS: The potency and maximal effects of (-)-norepinephrine at beta(1)-ARs (in the presence of beta(2)-AR blockade with 50 nM ICI 118,551 [erythro-DL-1(7-methylindan-4-yloxy)-3-isopropylamino-butan-2-ol]) for changes in contractile force and shortening of contractile cycle duration were determined in human right atrium in vitro from 87 patients undergoing coronary artery bypass grafting who were taking beta-blockers before surgery. A smaller sample of patients (n = 20) not taking beta-blockers was also investigated. Genotyping for two beta(1)-AR polymorphisms (Ser49Gly and Gly389Arg) was determined from a sample of blood taken at the time of surgery. RESULTS: (-)-Norepinephrine caused concentration-dependent increases in contractile force and reductions in time to reach peak force and time to reach 50% relaxation. There were no differences in the potency or maximal effects of (-)-norepinephrine in the right atrium from patients with different Ser49Gly and Gly389Arg polymorphisms. CONCLUSIONS: The cardiostimulant effects of (-)-norepinephrine at beta(1)-ARs were conserved across Ser49Gly and Gly389Arg polymorphisms in the right atrium of nonfailing hearts from patients with CAD managed with or without beta-blockers.

Adrenergic beta-1 Receptor Agonists↗

PubMed1996

Responses of plasma norepinephrine and renin-angiotensin-aldosterone system to dynamic exercise in patients with congestive heart failure.

BACKGROUND: Neurohormonal activation is present and neurohormonal responses to dynamic exercise are altered in congestive heart failure (CHF). Responses of plasma norepinephrine in various degrees of heart failure have been investigated, but the responses of the renin-angiotensin-aldosterone system have not been studied in relation to the severity of CHF. The aim of this study was to determine if the responses of the renin-angiotensin-aldosterone system to exercise are augmented according to the severity of CHF. METHODS AND RESULTS: Ventilatory and neurohormonal responses were assessed in 38 patients with CHF (New York Heart Association class: I, 13 patients; II, 14 patients; III, 11 patients) and 11 normal subjects during symptom-limited cardiopulmonary exercise testing. Plasma norepinephrine, renin activity, angiotensin II, and aldosterone were measured at rest and at peak exercise. The increments in neurohormones were divided by peak oxygen consumption, and these ratios (norepinephrine exercise ratio, plasma renin activity-exercise ratio, angiotensin II-exercise ratio, aldosterone-exercise ratio) were compared among groups. Peak oxygen consumption and anaerobic threshold decreased progressively with the severity of CHF. Neurohormonal profiles at rest showed that plasma norepinephrine levels were significantly higher, and the renin-angiotensin-aldosterone system was augmented only in patients with class III CHF. Neurohormones increased during exercise both in patients with CHF and in normal subjects, but patients with class III CHF had significantly higher plasma renin activity (10.11 +/- 2.32 ng/mL/h), angiotensin II (73.9 +/- 14.2 pg/mL), and aldosterone (265.2 +/- 61.1 pg/mL) than did normal subjects. Plasma renin activity-exercise ratio, angiotensin II-exercise ratio, and aldosterone-exercise ratio in patients with class III CHF were significantly higher compared to normal subjects. This augmentation of the renin-angiotensin-aldosterone system was not observed in class I or II patients. Peak plasma norepinephrine levels were not different among normal subjects and subgroups of CHF patients, but the norepinephrine-exercise ratio was significantly higher in classes II and III CHF compared to normal subjects. CONCLUSIONS: These data suggest that neurohormonal excitation during exercise increases along with the severity of CHF when normalized for peak exercise level.

Aldosterone↗