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Results for “Norepinephrine”

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PubMed1983

Increased norepinephrine release during sympathetic nerve stimulation and its inhibition by adenosine in the isolated perfused kidney of spontaneously hypertensive rats.

The present study was performed to measure norepinephrine release during sympathetic nerve stimulation and determine the inhibitory action of adenosine on stimulus-induced release of norepinephrine in the isolated perfused kidney of WKY and SHR. Norepinephrine release during periarterial nerve stimulation was measured as total 3H-overflow since greater than 75% of total 3H-overflow was 3H-norepinephrine in both the WKY and SHR. A significantly greater increase in 3H-norepinephrine overflow was observed during periarterial nerve stimulation in SHR in comparison with WKY. Adenosine (0.3, 1.0, 3.0 and 10.0 micrograms/ml) produced dose-dependent inhibition of 3H-norepinephrine overflow elicited by periarterial nerve stimulation. However, the effect of adenosine on transmitter release was more pronounced in the SHR in that the threshold dose required to cause inhibition of stimulus-induced release of 3H-norepinephrine was smaller in the SHR. These results demonstrate that while norepinephrine release during sympathetic nerve stimulation is greater in the SHR, this finding can not be explained on the basis of a decrease in the presynaptic inhibitory action of adenosine. Therefore, the mechanism responsible for the increased release of norepinephrine in the SHR remains to be determined.

Adenosine↗

PubMed1984

Postvagal potentiation of the chronotropic effect of norepinephrine.

Following termination of vagal stimulation, heart rate increases above control (postvagal tachycardia). This phenomenon has been attributed to vagally mediated release of norepinephrine in the sinus node region, although other contributory factors may be important. The possibility that, during the postvagal period, the chronotropic efficacy of norepinephrine is enhanced was investigated. Mongrel dogs (N = 6) were pretreated with reserpine in order to minimize postvagal tachycardia and hence allow reliable detection of enhanced responsiveness to norepinephrine. The dogs were then anesthetized with chloralose, autonomically decentralized, and instrumented to record electrocardiogram, aortic blood pressure, and electrograms from right atrium and right ventricle. Thirty-, forty-, or sixty-second infusions of norepinephrine were administered via the sinus node artery. The mean cycle length decrease produced by norepinephrine alone was 95 msec (which corresponds to a heart rate increase of + 19.6 bpm). After a 30-sec period of vagal stimulation, norepinephrine infusions produced a cycle length decrease of 139 msec (+32.5 bpm). These results are significant at the P less than 0.05 level. It is concluded that norepinephrine infusions produce a significantly greater magnitude of tachycardia when administered postvagally. It is proposed that this postvagal potentiation of the chronotropic effect of norepinephrine may contribute to postvagal tachycardia. Indeed, there may be a synergistic relationship between this phenomenon and vagally mediated release of norepinephrine in the mediation of postvagal tachycardia.

Animals↗

PubMed1975

Interaction of angiotensin with exogenous and neurally released norepinephrine on the cat nictitating membrane in vitro.

We have studied the effect of high (1-2.9 X 10(-5) M) and low 1.9 X 10(-9) M) concentrations of angiotensin on the retention and release of 3H-norepinephrine by the cat isolated nicititating membrane preparation in vitro in conjunction with their effect on the contractile responsiveness of the preparation to exogenous norepinephrine and transmural electrical stimulation. Both concentrations of angiotensin made the preparation contract, but only the high concentration affected the retention and spontaneous efflux of 3-H-norepinephrine. Retention was inhibited about 25% only when the preparation was preincubated with the angiotensin for 30 minutes (i.e., before adding 3H-norepinephrine). Under similar conditions cocaine, 2.9 X 10(-5) M, inhibited retention more than 90%. Spontaneous efflux was increased for as long as the high concentration of angiotensin was in contact with the preparation. Under similar conditions, tyramine, 5.7 X 10(-6) M, caused a much greater sustained increase in spontaneous efflux. Transmural stimulation of the preparation caused release of 3H-norepinephrine and frequency-dependent contractions. The contractions were selectively inhibited by phentolamine, 2.7 X 10(-6) M, or bretylium, 2.4 X 10(-5) M. Angiotensin had no effect on this neurally mediated 3H-norepinephrine release and contractile response or on contractions produced by exogenous norepinephrine. Since, as reported previously, angiotensin in vivo strongly inhibits contractile responses of the cat nicitating membrane to both neurally released and exogenous norepinephrine, the present results make it unlikely that such inhibition derives from angiotensin's relatively modest capacity for affecting the disposition of norepinephrine by this effector organ.

Angiotensin II↗

PubMed1992

Norepinephrine amplifies angiotensin II-induced vasoconstriction in rabbit femoral artery.

Several reports have focused on the ability of angiotensin II to amplify vascular contractile responses to norepinephrine, but none have determined whether norepinephrine enhances angiotensin II-induced vasoconstriction. Measuring isometric contraction in isolated rabbit femoral artery rings, we have found that the angiotensin II-induced contractile response was amplified in the presence of a threshold contraction to norepinephrine, as manifested by a 2.9-fold leftward shift of the midpoint of the concentration-response curve with no change in the maximal response. This amplification was attenuated markedly by nifedipine (0.1 microM), a calcium channel antagonist, implicating calcium channel activation in the amplification phenomenon. Precontracting the smooth muscle with a threshold concentration of angiotensin II had no enhancing effect on further angiotensin responses, indicating that the norepinephrine-induced amplification was due to a specific action of norepinephrine, rather than to a precontraction itself. In experiments in which the angiotensin II response was diminished by the presence of the noncompetitive angiotensin II antagonist [Sar1 Ala8]angiotensin II (0.3 microM), norepinephrine affected the angiotensin II response primarily by increasing the maximal response attainable. Prazosin (0.1 microM) both blocked the norepinephrine threshold contraction and abolished completely the amplification. However, when the norepinephrine concentration was increased until a threshold contraction was elicited in the presence of a fixed concentration of prazosin, amplification of the angiotensin II response was restored. These results indicate that norepinephrine exerts its amplifying effect on angiotensin II via activation of alpha-1 adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1991

Effect of dietary NaCl on norepinephrine turnover in the Dahl rat.

To evaluate neural mechanisms in salt-sensitive hypertension, norepinephrine turnover rates were measured in peripheral tissues and selected brain areas of Dahl salt-sensitive and salt-resistant rats receiving either 1% or 7% NaCl diets for 5 weeks. Norepinephrine turnover was determined by measuring tissue norepinephrine in untreated animals or in separate groups killed 2, 4, 6, and 10 hours after alpha-methyl-tyrosine. Plasma volume (radiolabeled albumin) was also measured. Arterial pressure of Dahl S rats receiving 7% NaCl (167 +/- 4 mm Hg) was higher (p less than 0.001) than that of Dahl S rats receiving 1% NaCl (141 +/- 3mm Hg), which was higher (p less than 0.001) than that of Dahl R rats receiving both NaCl intakes. Norepinephrine turnover was increased (p less than 0.01) by 7% NaCl in both heart and brown adipose tissue in Dahl S rats, whereas norepinephrine turnover in Dahl R rats was decreased (p less than 0.01) by the 7% NaCl intake in the heart and kidney. On the high NaCl intake, norepinephrine turnover in heart and adipose tissue was lower (p less than 0.05) in Dahl R rats than in Dahl S rats. In brain stem tissue, with the 1% NaCl diet, norepinephrine turnover was higher (p less than 0.001) in Dahl S rats than in Dahl R rats, and norepinephrine turnover was inhibited (p less than 0.001) by the high NaCl intake in Dahl S rats but not in Dahl R rats. In posterior hypothalamus, norepinephrine turnover was inhibited (p less than 0.01) by the high NaCl intake in Dahl R rats but not in Dahl S rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown↗

PubMed1991

Captopril increases norepinephrine spillover rate in conscious spontaneously hypertensive rats.

These experiments were designed to test the hypothesis that the antihypertensive action of the converting enzyme inhibitor captopril in conscious spontaneously hypertensive rats is associated with an inhibition of norepinephrine release from peripheral sympathetic neurons. Radiotracer techniques were used to measure norepinephrine clearance and spillover rate into plasma. A single 30 mg/kg (s.c.) dose of captopril elevated norepinephrine spillover rate by 20 to 25 and 45 to 60% at 0.5- and 2-hr postinjection, respectively. At 2-hr postinjection, captopril (10 and 30 mg/kg s.c.) produced a dose-related fall in mean arterial pressure (MAP) and dose-related increase in norepinephrine spillover rate. The 30-mg/kg dose was more effective in decreasing MAP when given s.c. as compared to i.v. dosing. When equivasodepressor doses of captopril, hydralazine and prazosin were compared at 2-hr postinjection, the increases in norepinephrine spillover rate produced by captopril (44%) and hydralazine (68%) were not different. However, prazosin elevated norepinephrine spillover rate by 137%. Norepinephrine clearance was not altered by captopril. When MAP was lowered to the same extent (-17 to -23%) by 5 days of continuous treatment with captopril, enalaprilat and minoxidil, the increases in norepinephrine spillover rate (50-65%) were not different in the three treatment groups. In conclusion, these data do not support the hypothesis that captopril lowers blood pressure by inhibiting the neuronal release of norepinephrine.

Animals↗

PubMed1984

Synthesis of phosphatidylcholines in rat hepatocytes. Possible regulation by norepinephrine via an alpha-adrenergic mechanism.

The effect of norepinephrine on phosphatidylcholine and phosphatidylethanolamine formation was investigated in short-term incubations with freshly isolated rat hepatocytes. In the presence of dl-propranolol, norepinephrine decreases the incorporation of [methyl-14C]choline into phosphatidylcholines in a dose-dependent manner. At a concentration of 50 microM, norepinephrine (plus 20 microM propranolol) inhibits the incorporation of [methyl-14C]choline over a wide range of choline concentrations (59% inhibition at 5 microM choline; 34% inhibition at 1 mM choline). Norepinephrine also decreases the incorporation rates of [1-14C]palmitic acid and [1-14C]oleic acid into phosphatidylcholines. The effect of norepinephrine is mediated through an alpha-adrenergic receptor. Norepinephrine (plus propranolol) does not decrease the uptake or phosphorylation rate of [methyl-14C]choline. Pulse-label and pulse-chase studies indicate that the conversion rate of phosphocholine to CDP-choline, catalyzed by CTP:phosphocholine cytidylyltransferase, is diminished by norepinephrine. In contrast with the inhibitory effect of norepinephrine on phosphatidylcholine synthesis, this hormone stimulates the formation of phosphatidylethanolamines from [1,2-14C]ethanolamine. This increased incorporation rate is apparent at ethanolamine concentrations above 25 microM. A combination of norepinephrine and propranolol decreases, however, the synthesis of phosphatidylcholines from [1,2-14C]ethanolamine. The results indicate that alpha-adrenergic regulation dissociates the synthesis of phosphatidylcholines from that of phosphatidylethanolamines.

Animals↗

PubMed1993

Binding of 3H-norepinephrine to receptors of pancreatic islets isolated from neonatal and adult rats.

Binding of 3H-norepinephrine to receptors and insulin release from pancreatic islets isolated from newborns and adult rats were investigated. In the presence of norepinephrine at the concentration of 2.4 x 10(-8) mol/l adults islets bound 0.37 +/- 0.11 fmol of norepinephrine per micrograms of islet protein while neonatal islets bound 0.25 +/- 0.08 fmol/micrograms. When norepinephrine concentration was raised to 10(-5) mol/l the amount of bound norepinephrine increased up to 22.66 +/- 8.7 fmol/micrograms and 14.20 +/- 5.36 fmol/micrograms for both examined groups, respectively. Addition of 5 x 10(-4) mol/l of phentolamine to the incubation medium induced 74% and 70% decrease of bound norepinephrine to adult and neonatal islets, respectively. At similar range of concentrations both norepinephrine and phentolamine modified the rate of insulin secretion and caused changes in binding of 3H-norepinephrine. There were no differences between the binding of norepinephrine to neonatal and adult islets. This may suggest that adrenergic system may play greater role in the regulation of insulin release from neonatal than from adult islets.

Animals↗

PubMed1996

Treatment with the type IV phosphodiesterase inhibitor Ro 20-1724 protects renal and mesenteric blood flow in endotoxemic rats treated with norepinephrine.

We recently reported that pretreatment with the type IV phosphodiesterase inhibitor Ro 20-1724 attenuates the development of endotoxin-induced acute renal failure in rats. Norepinephrine is an important therapeutic agent in human endotoxemia, but its efficacy is limited by its deleterious side effect of potent renal and mesenteric vasoconstriction. In this study we examined whether posttreatment with Ro 20-1724 after endotoxin infusion 1) attenuates increased renal vascular resistance and the development of acute renal failure in the absence and presence of norepinephrine infusion, 2) improves mesenteric blood flow in the presence of norepinephrine and 3) improves survival rates in the absence and presence of norepinephrine infusion. Forty-eight rats were anesthetized and instrumented, and eight 20-min clearance periods were performed. Endotoxin (20 mg/kg i.v.) was administered after the first period, and a constant-rate i.v. infusion of either Ro 20-1724 (10 micrograms/kg/min) or vehicle was initiated after period 3, in the absence and presence of norepinephrine infusion (1 microgram/kg/ min, begun after period 4). Urinary cAMP excretion in the Ro 20-1724-treated groups was 2- to 3-fold (P < .001) higher, compared with the vehicle-treated groups. Ro 20-1724 markedly attenuated endotoxin-induced (P < .01) increases in renal vascular resistance and attenuated norepinephrine-induced (P < .05) increases in renal vascular resistance in rats pretreated with endotoxin. Moreover, Ro 20-1724 reduced endotoxin-induced decreases in renal blood flow (P < .05) and glomerular filtration rate (P < .01) in the absence and presence of norepinephrine. In animals pretreated with endotoxin, Ro 20-1724 attenuated norepinephrine-induced increases in mesenteric vascular resistance (P = .054) and decreases in mesenteric blood flow (P < .01). Ro 20-1724 also improved survival rates for endotoxin-treated rats, whether or not the rats were administered norepinephrine (P < .01). Type IV-specific phosphodiesterase inhibitors warrant further study as selective therapeutic agents that protect against endotoxin/vasopressor-induced renal and mesenteric ischemia and death.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

PubMed1998

Aqueous humor flow in sleeping humans is unaffected by norepinephrine infusion.

PURPOSE: Intravenous administration of the catecholamine epinephrine is known to have a stimulatory effect on aqueous humor flow in sleeping human subjects, an effect that is augmented by plasma corticosteroids. This study was performed to determine whether the closely related catecholamine norepinephrine has a similar effect on aqueous humor flow. METHODS: Twenty normal subjects were studied. Aqueous flow was measured by fluorophotometry. At night during sleep, norepinephrine or placebo was infused intravenously (i.v.) between midnight and 6 AM. The rate of aqueous flow during the norepinephrine infusion was compared with the rate of flow during placebo infusion, with each subject serving as his/her own control. The urinary excretions of epinephrine and norepinephrine were measured at the end of each infusion period. RESULTS: The norepinephrine infusion caused an 8% increase in systolic blood pressure (P < 0.001), a 15% increase in diastolic blood pressure (P < 0.001), and a 9% decrease in heart rate (P=0.003) compared with the placebo. The rate of aqueous humor flow during sleep from 12 AM to 6 AM was unchanged by norepinephrine. The rate was 1.27+/-0.31 microl/min (mean+/-SD) during i.v. infusion of placebo and 1.30+/-0.27 microl/min during infusion of norepinephrine (P=0.63). CONCLUSIONS: An infusion of norepinephrine during sleep that causes measurable changes in cardiovascular parameters has no measurable effects on the rate of aqueous humor flow. The lack of a measurable effect of a norepinephrine infusion contrasts to the stimulatory effect of an epinephrine infusion.

Adult↗

PubMed1998

Regulation of extracellular dopamine by the norepinephrine transporter.

There is growing evidence of an interaction between dopamine and norepinephrine. To test the hypothesis that norepinephrine terminals are involved in the uptake and removal of dopamine from the extracellular space, the norepinephrine uptake blocker desmethylimipramine (DMI) was infused locally while the extracellular concentrations of dopamine were simultaneously monitored. DMI increased the extracellular concentrations of dopamine in the medial prefrontal cortex and nucleus accumbens shell but had no effect in the striatum. The combined systemic administration of haloperidol and the local infusion of DMI produced an augmented increase in extracellular dopamine in the cortex compared with the increase produced by either drug alone. This synergistic increase in dopamine overflow is likely due to the combination of impulse-mediated dopamine release produced by haloperidol and blockade of the norepinephrine transporter. No such synergistic effects were observed in the nucleus accumbens and striatum. Local perfusion of the alpha2-antagonist idazoxan also increased the extracellular concentrations of dopamine in the cortex. Although the stimulation of extracellular dopamine by idazoxan and DMI could be due to the increased extracellular concentrations of norepinephrine produced by these drugs, an increase in dopamine also was observed in lesioned rats that were depleted of norepinephrine and challenged with haloperidol. This contrasted with the lack of an effect of haloperidol on cortical dopamine in unlesioned controls. These results suggest that norepinephrine terminals regulate extracellular dopamine concentrations in the medial prefrontal cortex and to a lesser extent in the nucleus accumbens shell through the uptake of dopamine by the norepinephrine transporter.

Adrenergic alpha-Antagonists↗

PubMed2004

Cardiac uptake-1 inhibition by high circulating norepinephrine levels in patients with pheochromocytoma.

Neuronal reuptake (uptake-1) constitutes the main route of inactivation of the sympathetic neurotransmitter norepinephrine in the heart and therefore contributes importantly to cardiac sympathetic neuroeffector function. In laboratory animals and in vitro preparations, half saturation of the transporter occurs at norepinephrine concentrations of 0.1 to 1 micromol/L. This study addressed whether endogenous norepinephrine can attain high enough plasma concentrations in humans to inhibit cardiac uptake-1. Patients with increased plasma norepinephrine levels due to pheochromocytoma were assessed by 6-[18F]fluorodopamine positron emission tomography. Above an antecubital venous plasma concentration of 3 nmol/L (approximately 500 pg/mL), left ventricular myocardial 6-[18F]fluorodopamine-derived radioactivity varied inversely with the logarithm of the plasma norepinephrine concentration (r=-0.77, P<0.0001). Reduction of plasma norepinephrine levels by treatment of the pheochromocytoma increased myocardial 6-[18F]fluorodopamine-derived radioactivity. At sufficiently high plasma concentrations, endogenous norepinephrine can compete with sympathetic imaging agents for uptake-1. The results call for caution in drawing quantitative conclusions about uptake-1 in the setting of high circulating concentrations of endogenous norepinephrine.

Adrenal Gland Neoplasms↗

PubMed1999

Blockade of nitric oxide synthase potentiates the suppression of vasodilators by norepinephrine in the hepatic artery.

We have previously shown that nitric oxide (NO) and adenosine suppress vasoconstriction induced by norepinephrine infusion and sympathetic nerve stimulation in the hepatic artery and superior mesenteric artery. NO is involved in the control of basal vascular tone in the superior mesenteric artery but not the hepatic artery. The vasodilation induced by adenosine is inhibited by NO in the superior mesenteric artery but not in the hepatic artery. Based on these known interactions of catecholamines, adenosine, and NO, the objective of this study was to test the hypothesis that NO modulates the interaction between vasoconstrictors and vasodilators in the hepatic artery. We examined the ability of norepinephrine to suppress adenosine-mediated vasodilation and the role of NO in this interaction. Hepatic arterial blood flow and pressure were monitored in pentobarbital-anesthetized cats. The maximum hepatic arterial vasoconstrictor response to norepinephrine infusion was potentiated by blockade of NO production using Nomega-nitro-L-arginine methyl ester (L-NAME), and the potentiation was reversed by L-arginine. The maximum dilator response to adenosine was only slightly suppressed (14.0+/-5.8%, P < 0.05) by norepinephrine infusion; however, after the NO blockade, the suppression by norepinephrine of the vasodilation induced by adenosine was substantially potentiated (45.2+/-9.1%, P < 0.05). Similar results were obtained for isoproterenol-induced vasodilation. We conclude that the interaction between these vasodilators and norepinephrine was modulated by NO which inhibited the vasoconstriction and the suppression of vasodilators caused by norepinephrine and that in the absence of NO production, norepinephrine-induced constriction and the ability to antagonize dilation is substantially potentiated.

Adenosine↗

PubMed1984

Estimation of intrasynaptic norepinephrine concentrations at vascular neuroeffector junctions in vivo.

We estimated vascular neuroeffector junctional norepinephrine concentrations and their relation to pressor responses by measuring plasma norepinephrine levels and blood pressure during sympathetic stimulation or norepinephrine infusion in pithed, vagotomized, alpha 2-adrenoceptor blocked, adrenal-demedullated rats with and without uptake1 blockade by desipramine. For an increment in mean arterial pressure of 50 mm Hg, the estimated mean junctional norepinephrine concentration ( ES50m ) was about 7 nmol/l. Norepinephrine concentration gradients between the site of norepinephrine release and plasma appeared to be equal and reciprocal for sympathetic stimulation and for norepinephrine infusion. These gradients were reduced equally (by about two-thirds) after desipramine treatment, indicating that removal of both released and infused norepinephrine is mainly by neuronal uptake.

Animals↗

PubMed1994

Adrenergic, purinergic, and endothelial mediators and modulators of norepinephrine-induced mesenteric autoregulatory escape.

We evaluated the effects of potential factors in autoregulatory escape from norepinephrine-induced vasoconstriction in rat anterior mesenteric artery. We determined mesenteric artery blood flow velocity with a pulsed Doppler, sonic flowmeter, and systemic arterial blood pressure with a transducer. A 4-min norepinephrine infusion (0.125-1.0 x 10(-8) M/min) intravenously evoked a dose-dependent, initial vasoconstriction that was followed by rapid escape of blood flow toward or above the control value during sustained norepinephrine administration. Neonatal capsaicin treatment enhanced vasoconstrictor responses to norepinephrine but failed to affect escape parameters. Propranolol decreased norepinephrine-induced escape dose dependently. Adenosine deaminase attenuated escape, and the combination of this enzyme plus propranolol nearly abolished escape from norepinephrine-induced vasoconstriction. Methylene blue also diminished autoregulatory escape. These findings suggest that norepinephrine-induced autoregulatory escape involves simultaneous beta-adrenoceptor, purinergic, and endothelial mediation. Norepinephrine-evoked mesenteric vasoconstriction appears to involve predominantly alpha 2-adrenoceptors and is modulated by peptidergic sensory nerves and adenosine.

Adenosine Deaminase↗

PubMed1996

Norepinephrine contents of human prostatic hyperplasia: differences between pathological subtypes.

Tissue norepinephrine content in benign prostatic hyperplasia (BPH) was evaluated to detect possible histological differences in BPH subtypes and to investigate the correlation between norepinephrine levels and age, prostatic weight and clinical symptom score, respectively. Specimens were obtained from 28 patients who underwent transurethral resection of the prostate. Pathologically, 18 out of 28 specimens were classified as fibromyoadenomatous hyperplasia and the remaining 10 as fibromuscular type. Norepinephrine content in the fibromyoadenomatous type was 133.1 +/- 23.1 ng/g, whereas it was 340.3 +/- 60.5 ng/g in the fibromuscular type. Norepinephrine level in the former group was significantly lower than that in the latter group (p < 0.001). In both groups, there was no correlation between norepinephrine content, age and clinical symptom score, while the norepinephrine content had a reverse correlation with prostatic weight only in the former group (p < 0.05). In conclusion, norepinephrine levels were dependent upon histological differences, especially upon the amount of smooth muscle elements, in the evaluated specimen. Severity of prostatism and patients' age showed no correlation with tissue norepinephrine content.

Aged↗

PubMed2002

Norepinephrine-induced hyperglycemia does not increase cortical lactate in brain-injured rats.

OBJECTIVE: Hyperglycemia aggravates ischemic brain damage. Since catecholamines increase hepatic gluconeogenesis, resulting in hyperglycemia, we investigated whether norepinephrine and dopamine elevate arterial blood glucose, thereby increasing pericontusional cortical glucose and lactate concentrations and brain edema in brain-injured rats. DESIGN: Prospective, randomized, controlled animal study. SUBJECTS: Male Sprague Dawley rats. INTERVENTIONS: Physiological saline solution, norepinephrine, or dopamine were infused intravenously for 90 min beginning 4.5 h after inducing a focal cortical contusion. Blood glucose, lactate, and pericontusional cortical extracellular glucose and lactate were determined before, during and up to 60 min after the infusion period. Thereafter brains were removed to assess hemispheric water content. MEASUREMENTS AND RESULTS: Continuous norepinephrine and dopamine infusion significantly increased pericontusional glucose concentrations, being mostly sustained by norepinephrine (NaCl: 1.3+/-0.2, dopamine: 2.7+/-0.2, norepinephrine: 4.8+/-1.1 mM). While arterial blood glucose was only significantly elevated in norepinephrine-treated rats from 8.6+/-0.6 to 12.6+/-1.6 mM, the extracellular to blood glucose ratio was significantly increased in dopamine- and norepinephrine-treated rats (0.28+/-0.01 and 0.38+/-0.05 vs. 0.17+/-0.01). Plasma and pericontusional lactate remained unchanged, and brain edema was similar in all groups. CONCLUSIONS: Norepinephrine and dopamine significantly increased pericontusional glucose concentrations which did not elevate extracellular lactate and aggravate underlying posttraumatic edema formation. In addition to possibly increased facilitated endothelial glucose transport, the elevated extracellular to blood glucose ratio suggests a passive concentration- and pressure- dependent entry via a damaged blood-brain barrier. This might contribute to the observed reversible increase in extracellular glucose.

Animals↗

PubMed1997

Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study.

OBJECTIVES: To compare the effects of norepinephrine and dobutamine to epinephrine on hemodynamics, lactate metabolism, and gastric tonometric variables in hyperdynamic dopamine-resistant septic shock. DESIGN: A prospective, intervention, randomized clinical trial. SETTING: Adult medical/surgical intensive care unit in a university hospital. PATIENTS: 30 patients with a cardiac index (CI) > 3.51 x min(-1) x m(-2) and a mean arterial pressure (MAP) < or = 60 mmHg after volume loading and dopamine 20 microg/kg per min and either oliguria or hyperlactatemia. INTERVENTIONS: Patients were randomized to receive an infusion of either norepinephrine-dobutamine or epinephrine titrated to obtain an MAP greater than 80 mmHg with a stable or increased CI. MEASUREMENTS AND MAIN RESULTS: Baseline measurements included: hemodynamic and tonometric parameters, arterial and mixed venous gases, and lactate and pyruvate blood levels. These measurements were repeated after 1, 6, 12, and 24 h. All the patients fulfilled the therapeutic goals. No statistical difference was found between epinephrine and norepinephrine-dobutamine for systemic hemodynamic measurements. Considering metabolic and tonometric measurements and compared to baseline values, after 6 h, epinephrine infusion was associated with an increase in lactate levels (from 3.1 +/- 1.5 to 5.9 +/- 1.0 mmol/l;p < 0.01), while lactate levels decreased in the norepinephrine-dobutamine group (from 3.1 +/- 1.5 to 2.7 +/- 1.0 mmol/l). The lactate/pyruvate ratio increased in the epinephrine group (from 15.5 +/- 5.4 to 21 +/- 5.8; p < 0.01) and did not change in the norepinephrine-dobutamine group (13.8 +/- 5 to 14 +/- 5.0). Gastric mucosal pH (pHi) decreased (from 7.29 +/- 0.11 to 7.16 +/- 0.07; p < 0.01) and the partial pressure of carbon dioxide (PCO2) gap (tonometer PCO2-arterial PCO2) increased (from 10 +/- 2.7 to 14 +/- 2.7 mmHg; p < 0.01) in the epinephrine group. In the norepinephrine-dobutamine group pHi (from 7.30 +/- 0.11 to 7.35 +/- 0.07) and the PCO2 gap (from 10 +/- 3.0 to 4 +/- 2.0 mmHg) were normalized within 6 h (p < 0.01). The decrease in pHi and the increase in the lactate/pyruvate ratio in the epinephrine group was transient, since it returned to normal within 24 h. CONCLUSIONS: Considering the global hemodynamic effects, epinephrine is as effective as norepinephrine-dobutamine. Nevertheless, gastric mucosal acidosis and global metabolic changes observed in epinephrine-treated patients are consistent with a markedly inadequate, although transient, splanchnic oxygen utilization. The metabolic and splanchnic effects of the combination of norepinephrine and dobutamine in hyperdynamic dopamine-resistant septic shock appeared to be more predictable and more appropriate to the current goals of septic shock therapy than those of epinephrine alone.

Adrenergic beta-Antagonists↗