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Results for “Norepinephrine”

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At least 289 records · Page 16Linked to original sources

PubMed2004

Histamine H3-receptor-induced attenuation of norepinephrine exocytosis: a decreased protein kinase a activity mediates a reduction in intracellular calcium.

We had reported that activation of presynaptic histamine H(3)-receptors inhibits norepinephrine exocytosis from depolarized cardiac sympathetic nerve endings, an action associated with a marked decrease in intraneuronal Ca(2+) that we ascribed to a decreased Ca(2+) influx. An H(3)-receptor-mediated inhibition of cAMP-dependent phosphorylation of Ca(2+) channels could cause a sequential attenuation of Ca(2+) influx, intraneuronal Ca(2+) and norepinephrine exocytosis. We tested this hypothesis in sympathetic nerve endings (cardiac synaptosomes) expressing native H(3)-receptors and in human neuroblastoma SH-SY5Y cells transfected with H(3)-receptors. Norepinephrine exocytosis was elicited by K(+) or by stimulation of adenylyl cyclase with forskolin. H(3)-receptor activation markedly attenuated the K(+)- and forskolin-induced norepinephrine exocytosis; pretreatment with pertussis toxin prevented this effect. Similar to forskolin, 8-bromo-cAMP elicited norepinephrine exocytosis but, unlike forskolin, it was unaffected by H(3)-receptor activation, demonstrating that inhibition of adenylyl cyclase is a pivotal step in the H(3)-receptor transductional cascade. Indeed, we found that H(3)-receptor activation attenuated norepinephrine exocytosis concomitantly with a decrease in intracellular cAMP and PKA activity in SH-SY5Y-H(3) cells. Moreover, pharmacological PKA inhibition acted synergistically with H(3)-receptor activation to reduce K(+)-induced peak intracellular Ca(2+) in SH-SY5Y-H(3) cells and norepinephrine exocytosis in cardiac synaptosomes. Furthermore, H(3)-receptor activation synergized with N- and L-type Ca(2+) channel blockers to reduce norepinephrine exocytosis in cardiac synaptosomes. Our findings suggest that the H(3)-receptor-mediated inhibition of norepinephrine exocytosis from cardiac sympathetic nerves results sequentially from H(3)-receptor-G(i)/G(o) coupling, inhibition of adenylyl cyclase activity, and decreased cAMP formation, leading to diminished PKA activity, and thus, decreased Ca(2+) influx through voltage-operated Ca(2+) channels.

Adenylyl Cyclases↗

PubMed2002

EctoNucleotidase in cardiac sympathetic nerve endings modulates ATP-mediated feedback of norepinephrine release.

ATP, coreleased with norepinephrine, affects adrenergic transmission by acting on purinoceptors at sympathetic nerve endings. Ectonucleotidases terminate the actions of ATP. Previously, we had preliminary evidence for ectonucleotidase activity in cardiac sympathetic nerve terminals. Therefore, we investigated whether this ectonucleotidase might influence norepinephrine release in the heart. Sympathetic nerve endings isolated from guinea pig heart (cardiac synaptosomes) were rich in Ca(2+)-dependent ectonucleotidase activity, as measured by metabolism of exogenously added radiolabeled ATP or ADP. By its inhibitor profile, ectonucleotidase resembled ectonucleoside triphosphate diphosphohydrolase 1 (E-NTPDase1). Exogenous ATP elicited concentration-dependent norepinephrine release from cardiac synaptosomes (EC(50) 0.96 microM). This release was antagonized by the P2X receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) (10 microM) and potentiated by the P2Y receptor antagonist 2'-deoxy-N(6)-methyladenosine-3',5'-diphosphate (MRS 2179) (30 nM). Norepinephrine release promoted by ATP was also potentiated by the nucleotidase inhibitor 6-N,N-diethyl-beta-gamma-dibromomethylene-D-adenosine-5'-triphosphate (ARL67156) (30 microM) and blocked by a recombinant, soluble form of human E-NTPDase1 (solCD39). In contrast, ARL67156 had no effect on norepinephrine release induced by the nonhydrolyzable analog, alpha, beta-methyleneadenosine-5'-triphosphate (alpha,beta-MeATP). Depolarization of cardiac synaptosomes with K(+) elicited release of endogenous norepinephrine. This was attenuated by PPADS and solCD39 and potentiated by MRS 2179 and ARL67156. Importantly, our results demonstrate that facilitation of ATP-induced norepinephrine release from cardiac sympathetic nerves is a composite of two autocrine components: positive, mediated by P2X receptors, and negative, mediated by P2Y receptors. Modulation of norepinephrine release by coreleased ATP is terminated by endogenous as well as exogenous ectonucleotidase. We propose that ectonucleotidase control of norepinephrine release should provide cardiac protection in hyperadrenergic states such as myocardial ischemia.

5'-Nucleotidase↗

PubMed2004

Receptors subtypes involved in adenosine-mediated modulation of norepinephrine release from cardiac nerve terminals.

The objective of this study was to determine which adenosine receptor subtypes were involved in the modulation of norepinephrine release from cardiac nerve terminals. In addition, the persistence of adenosine-mediated effects was evaluated. Rat hearts attached to the stellate ganglion were isolated and perfused. The ganglion was electrically stimulated twice (S1 and S2), allowing 10 min between the stimulations. To determine adenosine receptor subtypes, selective and nonselective adenosine agonists and antagonists were infused following S1 and until the end of S2. To evaluate the persistence of adenosine-mediated effect on norepinephrine release, the stellate ganglion was stimulated a third (S3) and fourth (S4) time. Coronary effluents were collected to determine norepinephrine content. Adenosine and a selective A1 receptor agonist, CCPA, inhibited norepinephrine release by 49% and 54%, respectively. This effect was reversed by simultaneous infusion of nonspecific (8-SPT) and specific (DPCPX) A1 receptor antagonists. Selective A2A (CGS 21680) and A3 (AB-MECA) receptor agonists had no discernible effect on norepinephrine release. Similarly, adenosine A2A receptor antagonists CSC and DMPX did not alter the dose-response relation between norepinephrine release and adenosine. Finally, the inhibitory effects of adenosine on norepinephrine release did not persist 10 min subsequent to the removal of adenosine. Adenosine inhibited norepinephrine release primarily via the adenosine A1 receptor. This effect of adenosine was of short duration. Adenosine A2A and A3 receptors were either absent or functionally insignificant in the regulation of norepinephrine release in the rat heart.

Adenosine↗

PubMed1984

Norepinephrine-stimulated vascular prostacyclin synthesis. Receptor-dependent calcium channels control prostaglandin synthesis.

Norepinephrine-stimulated prostacyclin synthesis was studied in rat aortic rings by measuring 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) by radioimmunoassay. Norepinephrine (10(-6) M) results in a 10- to 20-fold increase in 6-keto-PGF1 alpha synthesis by rat aortic rings (54 +/- 11 to 437 +/- 260 pg X mg wet weight-1 X 20 min-1). The maximal stimulation of 6-keto-PGF1 alpha synthesis was observed with a norepinephrine concentration of 10(-5) M at a mean effective concentration (EC50) of 9.5 +/- 3.2 X 10(-7) M which is similar to the contractile response (Emax = 10(-5) M, EC50 = 6.5 +/- 1.8 X 10(-7) M). Potassium chloride (30 mM), although causing a similar maximal contractile response as 10(-6) M norepinephrine, did not increase 6-keto-PGF1 alpha synthesis. Norepinephrine-stimulated 6-keto-PGF1 alpha synthesis was dependent upon extracellular calcium. Norepinephrine stimulation in Ca2+-free medium did not lead to a significant increase in 6-keto-PGF1 alpha synthesis. However, on the introduction of Ca2+, 6-keto-PGF1 alpha synthesis was restored to its initial level. Phentolamine (10(-6) M) (an alpha-adrenergic antagonist) and trifluroperazine (2.5 X 10(-4) M) (a calmodulin inhibitor) completely inhibited norepinephrine-stimulated 6-keto-PGF1 alpha synthesis, whereas verapamil 3 X 10(-6) M (a calcium channel blocking drug) only partially inhibited synthesis (control, 74 +/- 12; norepinephrine, 437 +/- 260; norepinephrine + verapamil, 123 +/- 8 pg X mg wet weight-1 X 20 min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

PubMed1983

Renal venous outflow and urinary excretion of norepinephrine, epinephrine, and dopamine during graded renal nerve stimulation.

The effect of renal nerve stimulation (RNS) on renal venous outflow and urinary excretion of endogenous norepinephrine, epinephrine, and dopamine was examined in anesthetized dogs. In the unstimulated denervated kidney, there was a negative venoarterial concentration difference for all catecholamines. Low-level RNS (LLRNS) caused small changes in renal hemodynamics and renal venous outflow of dopamine and increased norepinephrine outflow by 3.22 +/- 0.95 pmol X min-1 X g-1 (n = 5, P less than 0.05). High-level RNS (HLRNS) reduced renal blood flow by 50% and increased renal venous outflow of norepinephrine and dopamine by 9.58 +/- 0.67 and 0.46 +/- 0.05 pmol X min-1 X g-1, respectively (n = 27, P less than 0.01 for both). Renal uptake of epinephrine was unchanged by HLRNS. The urinary excretion of norepinephrine but not dopamine was increased to a similar degree following RNS at both levels. HLRNS caused a similar increase of the urinary norepinephrine excretion from the contralateral denervated and unstimulated kidney. This could be explained by the increase in arterial norepinephrine (from 0.74 +/- 0.08 to 1.20 +/- 0.14 nM, P less than 0.01) caused by HLRNS as shown by experiments with intravenous infusions of norepinephrine. The alpha-adrenoceptor antagonist phenoxybenzamine counteracted the hemodynamic response to HLRNS and enhanced the renal venous outflow and urinary excretion of norepinephrine and dopamine. Our results indicate that renal nerves release dopamine as well as norepinephrine and that urinary catecholamine excretion is a poor indicator of intrarenal catecholamine release.

Animals↗

PubMed1988

Effect of norepinephrine on consumption of oxygen in perfused skeletal muscle from cold-exposed rats.

The effect of norepinephrine on the consumption of O2 was studied in the skeletal muscle in the perfused hindlimbs of rats that had been kept at 4 degrees C for 5-25 days. 1) Basal rates of consumption of O2 and release of lactate were not affected by exposure to cold. 2) The stimulation of consumption of O2 by norepinephrine increased in the perfused hindlimbs of rats exposed to cold for 10-25 days, with a maximum stimulation at 20 days. The response to norepinephrine decreased markedly in hindlimbs perfused with propranolol or phentolamine. Phenylephrine, in the presence of 0.5 nM isoproterenol, stimulated the consumption of O2 at concentrations as low as 0.5 microM, with a maximum at 5 microM, in hindlimbs from the group exposed to cold for 20 days. 3) Ouabain inhibited the stimulation of consumption of O2 by norepinephrine. Norepinephrine caused a net release of K+ in control muscle but a net uptake of K+ by muscle from the group exposed to cold for 20 days. The results suggest that the calorigenic responsiveness to norepinephrine increases in skeletal muscle during acclimation of the rat to the cold, both alpha- and beta-adrenergic actions are involved in the calorigenic effects of norepinephrine, and the increased activity of the Na+-K+ ATPase under the influence of norepinephrine may be involved in the calorigenic action of norepinephrine on the skeletal muscle of cold-acclimated rats.

Acclimatization↗

PubMed1989

Handling of tracer norepinephrine by the dog liver.

Norepinephrine handling by the dog liver was appraised by carrying out tracer-transient, multiple-indicator-dilution studies within steady-state conditions in a basal situation, during norepinephrine infusion and after the uptake inhibitor desipramine. In controls, tracer norepinephrine extraction averaged 61%, whereas bulk norepinephrine extraction was approximately 31%; intrahepatic secretion of unlabeled norepinephrine accounted for the difference. Infusion of norepinephrine, raising arterial levels more than an order of magnitude, constricted the hepatic vascular space but did not change tracer extraction; norepinephrine secretion remained essentially unchanged, and with this, bulk extraction approached tracer extraction. A theoretical analysis of norepinephrine uptake was developed. Analysis of tracer data with this indicated that the permeability surface products for influx and efflux, expressed per gram liver, did not change. Desipramine did not affect the uptake kinetics, indicating that the uptake process was virtually completely nonneurogenic. Late efflux of tracer normetanephrine product was detected but was small prior to recirculation. The study demonstrates that norepinephrine secretion ordinarily coexists with uptake and provides an approach to quantitating both.

Animals↗

PubMed1989

Norepinephrine release and reuptake by hypothalamic synaptosomes of spontaneously hypertensive rats.

We compared the overflow of endogenous norepinephrine during electrical field stimulation, the norepinephrine content, and the rate of initial neuronal uptake of [3H]norepinephrine in synaptosomes isolated from hypothalamus and brainstem of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at 7 and 13 weeks of age. The synaptosomes of two rats, a SHR and a WKY rat control, were simultaneously processed and subjected to the same electrical field stimulation. The overflow of endogenous norepinephrine during electrical stimulation (2 Hz, 2 minutes) in the hypothalamic synaptosomes of 7-week-old SHR was significantly greater, whereas the overflow of 13-week-old SHR was equivalent to the age-matched WKY rat. The norepinephrine content of synaptosomes was about the same in SHR and age-matched controls. There was also significantly enhanced [3H]norepinephrine uptake in the hypothalamic synaptosomes of young SHR, but neither the hypothalamic nor the brainstem samples of 13-week-old SHR showed any significant difference in their rate of [3H]norepinephrine uptake. These data are similar to those we observed (unpublished observations) in perfused mesenteric artery system in which norepinephrine release was significantly elevated during periarterial nerve stimulation only in young SHR. Thus, these results suggest that a parallel enhancement of norepinephrine release in hypothalamus with that of peripheral nervous system may play an important role during development of hypertension in young SHR.

Aging↗

PubMed1990

Norepinephrine release and neuropeptide Y in medulla oblongata of spontaneously hypertensive rats.

Neuropeptide Y is colocalized with norepinephrine in both central and peripheral noradrenergic neurons. In this study, we examined the regulatory mechanisms of neuropeptide Y on norepinephrine release in the medulla oblongata of rats. Neuropeptide Y inhibited the stimulation-evoked [3H]norepinephrine release in a dose-dependent manner in slices of medulla oblongata of Sprague-Dawley rats (1 Hz, S2/S1 ratio, control, 0.946 +/- 0.040 [+/- SEM], n = 6; neuropeptide Y 1 x 10(-8) M, 0.676 +/- 0.022, n = 6, p less than 0.05; neuropeptide Y 1 x 10(-7) M, 0.589 +/- 0.014, n = 6, p less than 0.05). Neuropeptide Y potentiated inhibition of [3H]norepinephrine release by the alpha 2-agonists UK 14,304 and clonidine. The blockade of alpha 2-adrenergic receptors by RX 781,094 diminished inhibitory effects of neuropeptide Y on norepinephrine release. Pretreatment of pertussis toxin (a toxin that interferes with the coupling of inhibitory receptors to adenylate cyclase) attenuated the suppression of norepinephrine release by neuropeptide Y. In spontaneously hypertensive rats, the inhibitory effect of UK 14,304 and neuropeptide Y on norepinephrine release from the medulla oblongata was significantly less than in age-matched Wistar-Kyoto rats. These results show that neuropeptide Y inhibits norepinephrine release partially mediated by alpha 2-adrenergic receptors and the pertussis toxin-sensitive guanosine triphosphate-binding proteins in rat medulla oblongata. Furthermore, less suppression of norepinephrine release by UK 14,304 and neuropeptide Y in spontaneously hypertensive rats suggests that alpha 2-adrenergic receptors and neuropeptide Y might be involved in the regulation of central sympathetic tone in hypertension.

Adenylate Cyclase Toxin↗

PubMed1996

Acute saline infusion decreases norepinephrine release in the anterior hypothalamic area.

Ingestion of a high NaCl diet elevates arterial pressure in spontaneously hypertensive rats, at least in part, by reducing the release of norepinephrine in the anterior hypothalamic area. The mechanism by which dietary NaCl excess alters anterior hypothalamic area norepinephrine release is unknown. Plasma Na+ is slightly elevated after ingestion of a meal; therefore, in the present study we tested the hypothesis that a small increase in plasma Na+ could reduce the release of norepinephrine in the anterior hypothalamic area and elevate arterial pressure. Male spontaneously hypertensive rats were randomized to be fed a diet containing either 1% (basal) or 8% (high) NaCl at age 7 weeks and were maintained on the diets for 2 weeks. Age-matched normotensive Wistar-Kyoto rats received a basal NaCl diet only. All rats were instrumented with a push/pull cannula, and 5 days later, the baseline release of 3-methoxy-4-hydroxyphenyl glycol (the major metabolite of norepinephrine in brain) was measured in awake, freely moving rats. Rats were then challenged with an intravenous infusion (75 microL/min) of hypertonic (2.7%) saline for 20 minutes. In spontaneously hypertensive rats fed a basal NaCl diet, the hypertonic saline infusion elevated mean arterial pressure by 12% and reduced the concentration of the norepinephrine metabolite in the anterior hypothalamic area by 19%; these alterations persisted after termination of the hypertonic saline infusion. Spontaneously hypertensive rats maintained on the high NaCl diet showed greatly reduced arterial pressure and norepinephrine metabolite responses. In normotensive control rats compared with the hypertensive rats fed the basal NaCl diet, the hypertonic saline had considerably less effects on arterial pressure and norepinephrine metabolite levels in the anterior hypothalamic area, and the responses were significantly shorter. Thus, a small elevation in plasma Na+ can reduce the release of norepinephrine in the anterior hypothalamic area. This response is greatly exaggerated in spontaneously hypertensive rats fed a basal (but not a high) NaCl diet, suggesting that a postprandial rise in NaCl could initiate the fall in norepinephrine and thereby contribute to the rise in arterial pressure in spontaneously hypertensive rats ingesting a high NaCl diet.

Animals↗

PubMed1976

Inhibition by acetylcholine of the norepinephrine release evoked by potassium in canine saphenous veins.

In the dog's saphenous vein acetylcholine inhibits the norepinephrine release caused by nerve stimulation, but not that caused by tyramine. Experiments were performed to determine whether acetylcholine affects the release of norepinephrine evoked by high K+ concentrations. We recorded changes in isometric tension of dog saphenous vein strips. Acetylcholine (5 X 10(-9) to 10(-6) g/ml) caused dose-dependent relaxations during contractions caused by K+ = 40 mEq/liter. These relaxations were not depressed by tetrodotoxin (10(-7) g/ml), which abolished the response to nerve stimulation, but were inhibited by atropine (10(-7) g/ml). Strips of saphenous veins were incubated with [3H]norepinephrine and mounted for superfusion (3 ml/min) and isometric tension recording; the total radioactivity and the amount of intact [3H]norepinephrine present in the superfusate were determined. K+ at 50 mEq/liter increased tension, total radioactivity of the superfusate, and the [3H]norepinephrine afflux; acetylocholine (10(-7) g/ml) depressed the contractions and diminished the efflux of [3H]norepinephrine. Increasing the K+ concentration from 50 to 70 mEq/liter augmented both tension and the evoked release of [3H]norepinephrine. Acetylcholine did not significantly alter the release of [3H]norepinephrine evoked by K+ = 120mEq/liter. These experiments show that acetylcholine inhibits the norepinephrine release evoked by potassium ions, as it does during nerve stimulation. The inhibition of adrenergic neurotransmission is not due to interference with action potential electrogenesis, but probably is caused by hyperpolarization of the adrenergic nerve endings.

Acetylcholine↗

PubMed1968

Norepinephrine inhibition of vasopressin antidiuresis.

The effect of norepinephrine on exogenous vasopressin antidiuresis was investigated in water-loaded subjects. After an initial 2 to 3 hr period of water loading (phase 1), 10-100 mU of vasopressin per hr were infused at a constant rate for 1 hr (phase 2) followed by infusion of 10-100 mU of vasopressin per hr plus 600 mug of l-norepinephrine per hr for 1 hr (phase 3). Endogenous creatinine clearance, osmolal clearance, and free water clearance (in milliliters/minute) and sodium and chloride excretion (in milliequivalents/minute) were measured. In 10 subjects given 10-20 mU of vasopressin per hr during phases 2 and 3, free water clearance decreased significantly from phase 1 to phase 2 (9.3 to 0.15, P = 0.001) and increased during phase 3 norepinephrine infusion to 4.7 ml/min (P = 0.001). A comparable decrease in phase 2 free water clearance was observed in four subjects given 50 or 100 mU of vasopressin per hr during phases 2 and 3 (P < 0.01); however, the phase 3 norepinephrine infusion in these subjects was not associated with an increase in free water clearance. Creatinine clearance, osmolal clearance, and sodium and chloride excretion were unchanged throughout the studies in both groups of subjects.A two phase study in seven subjects confirmed that 10, 20, or 75 mU of vasopressin per hr susstained antidiuresis during phase 2 for at least 2 hr and that free water clearance values were essentially constant in the individual subject after the first 30 min of infusion. The magnitude of the (phase 3) norepinephrine-induced increase in free water clearance (4.5 +/- 0.64 ml/min) during infusion of 10-20 mU of vasopressin per hr, the failure of norepinephrine to increase free water clearance during infusion of 50-100 mU of vasopressin per hr, and the relatively constant endogenous creatinine and osmolal clearance rates would suggest that the norepinephrine inhibition of vasopressin antidiuresis was not the result of alterations in renal blood flow. A post-phase 3 infusion of vasopressin in four subjects resulted in a marked decrease in free water clearance, indicating that the norepinephrine inhibition of vasopressin antidiuresis was not accountable on the basis of decreased medullary hypertonicity. These data support the hypothesis that catecholamine blocks the cellular mechanism of vasopressin antidiuresis in vivo. The observation that norepinephrine did not inhibit the antidiuresis produced by the infusion of 50 or 100 mU of vasopressin per hr suggests that this inhibition might be competitive. A possible role of catecholamine in the mechanism of cold diuresis is suggested.

Adult↗

PubMed1993

Detection by in vivo microdialysis of nicotine-induced norepinephrine secretion from the hypothalamic paraventricular nucleus of freely moving rats: dose-dependency and desensitization.

The ACTH response to many stimuli depends on the secretion of norepinephrine, which activates neurons in the hypothalamic paraventricular nucleus (PVN). Studies with adrenergic antagonists and inhibitors of catecholamine synthesis indicate that norepinephrine is a mediator of nicotine-induced ACTH secretion. To directly assess the effect of nicotine on PVN norepinephrine secretion, in vivo microdialysis was performed. Nicotine (0.5 mg/kg BW, ip) induced peak norepinephrine levels within 20 min (approximately 2 x basal). The central nicotinic receptor antagonist, mecamylamine, abolished this response, whereas hexamethonium, a peripheral antagonist, was ineffective. The norepinephrine response was dose dependent (ED50, approximately 0.25 mg/kg), and nicotine (0.5 mg/kg BW) induced maximal secretion. Rapid desensitization occurred, as evidenced by a significant reduction (approximately 50%) in the response to a second injection of nicotine (0.5 mg/kg BW). Animals also received four injections of nicotine to determine whether repetitive dosing leads to progressive reduction of the norepinephrine response. The responses to the third and fourth nicotine injections were similar. Thus, desensitization occurred after a single exposure to nicotine and was not progressive. In contrast, nicotine pretreatment did not affect the release of norepinephrine due to yohimbine. These results indicate that basal and nicotine-stimulated levels of norepinephrine can be detected in microdialysates from the PVN; rapid desensitization of the norepinephrine response to nicotine and inhibition by mecamylamine, but not hexamethonium, parallel the findings previously reported for ACTH.

Adrenocorticotropic Hormone↗

PubMed1982

Norepinephrine increases canine skeletal muscle VO2 during recovery.

The purpose of this study was to investigate the effect of norepinephrine on the rate of O2 uptake (VO2) of the denervated canine gastrocnemius-plantaris muscle group in situ. In seven experiments, VO2 and developed tension were measured without and with norepinephrine infusion during rest, during contractions at 1.0 Hz, and during recovery. In six additional experiments with two consecutive rest-contraction-recovery periods, no norepinephrine was given during the second sequence. During rest, VO2 was increased by norepinephrine. Changes in VO2 during contractions were small, but the arteriovenous O2 content difference was significantly greater during norepinephrine infusion. The most significant finding was that net recovery VO2 was increased 40% by norepinephrine infusion. The ratio of net recovery VO2 to the VO2 during the preceding contraction period was significantly increased from 0.78 +/- 0.07 (mean +/- SEM) to 1.23 +/- 0.07 (mean +/- SEM) by norepinephrine infusion. This increase in net recovery VO2 could be due to either a direct metabolic effect of norepinephrine during recovery or to hypoxia during the preceding contractions. In either case, the data indicated that norepinephrine can produce large increases in muscle recovery VO2; this supports the notion that catecholamines may make a significant contribution to post-exercise recovery VO2.

Animals↗

PubMed1989

Effect of dopamine vs norepinephrine on hemodynamics in septic shock. Emphasis on right ventricular performance.

The effects of continuously infused dopamine and norepinephrine on hemodynamics, oxygen metabolism, and right ventricular (RV) performance were studied by crossover design in ten patients with septic shock who needed treatment with vasoactive drugs after fluid replacement. Standard hemodynamic measurements were obtained and RV performance assessed before and 1 h after the start of the infusion. All but one patient had pulmonary hypertension, and in seven the RV ejection fraction (RVEF) was lower than 50 percent at baseline. Drugs were titrated to a systolic arterial blood pressure of mean 106 +/- 18 mm Hg for dopamine and 116 +/- 20 mm Hg for norepinephrine (NS). Dopamine infusion increased the cardiac index (CI) 16 percent (p less than 0.02), but heart rate and systemic and pulmonary vascular resistances were unchanged. With norepinephrine CI was unchanged, a heart rate decreased 7 percent (p less than 0.05), and systemic and pulmonary vascular resistance increased 35 and 26 percent, respectively (p less than 0.05). With both drugs, RV volumes and RVEF remained unchanged, and systemic oxygen consumption increased equally (by 19 percent for dopamine and 22 percent for norepinephrine, p less than 0.05); systemic oxygen delivery rose by 17 percent during dopamine infusion and was unchanged during norepinephrine infusion. Norepinephrine increased oxygen extraction vs dopamine (p less than 0.05). There were no differences in urinary output. Norepinephrine may improve the RV oxygen supply/demand ratio, but this potentially beneficial effect on RV ejection fraction may be offset by a concomitant increase in pulmonary vascular resistance and RV afterload. Norepinephrine may not adversely affect the peripheral circulation. In short-term treatment of volume-resuscitated, severe septic shock complicated by pulmonary hypertension and impaired RV performance, norepinephrine may be at least as effective as dopamine.

Adult↗

PubMed1979

Possible role of brain norepinephrine in the hypothalamic hypophyseal adrenal system.

Intracisternal injection of bethanidine in rats decreased brain norepinephrine turnover without affecting its endogenous level, and increased both cardiac norepinephrine turnover and serum corticosterone level. A negative correlation was observed between brain norepinephrine turnover rate and serum corticosterone level. On the other hand, when cardiac norepinephrine turnover was suppressed by intraperitoneal injection of bethanidine, serum corticosterone did not change significantly. Next, ether inhalation was added after intracisternal injection of bethanidine. Then, serum corticosterone increased more even brain norepinephrine turnover was suppressed only slightly. These data may indicate that serum corticosterone increases by selective decrease in brain norepinephrine turnover via the humoral route; from the hypothalamus down to the adrenal cortex. Inversely, intracisternal injection of corticosterone increased brain norepinephrine turnover. These results suggest that brain norepinephrine may play an inhibitory role in the tonic regulation of CRF-ACTH secretion in the higher center than the hypothalamus and there may be a closed-loop feedback system between brain norepinephrine and serum corticosterone.

Animals↗

PubMed2004

Dopamine reuptake by norepinephrine neurons: exception or rule?

Dopamine reuptake by norepinephrine terminals can occur in brain areas such as the prefrontal cortex, the nucleus accumbens shell, and the bed nucleus of stria terminalis that are innervated, although unevenly, by both dopamine and norepinephrine neurons. Therefore the antidepressants that bind selectively the norepinephrine transporter might produce their therapeutic effect by raising the extracellular concentration of dopamine besides that of norepinephrine. Moreover, cocaine can be reinforcing even in knock-out mice for the dopamine transporter because it might raise synaptic dopamine in the nucleus accumbens shell by preventing its uptake by the norepinephrine transporter, an effect that could take place even in wild animals. Recently, it has also been suggested that dopamine can be co-released with norepinephrine by norepinephrine neurons, although it is not clear whether this feature might be related to a previous nonspecific uptake of dopamine by the norepinephrine transporter. In this review we discuss the potential role of the nonspecific uptake of dopamine by norepinephrine transporter in the mechanism of action of drugs of abuse, antipsychotics, and antidepressants.

Animals↗

PubMed1985

Effect of norepinephrine on ketogenesis, fatty acid oxidation, and esterification in isolated rat hepatocytes.

Recent studies in man demonstrated a marked ketogenic effect of increased plasma norepinephrine concentrations as observed in diabetic ketoacidosis. Since this effect may have been due either to increased substrate supply for ketogenesis (lipolysis) or to direct hepatic activation of ketogenesis, the latter mechanism was examined in isolated rat hepatocytes. Incubation of hepatocytes with norepinephrine (10(-7) to 10(-4) M) resulted in a dose-dependent increase in conversion of the long-chain fatty acid [1-14C]palmitate into ketone bodies and CO2. Norepinephrine decreased [1-14C]palmitate conversion into triglycerides without affecting fatty acid uptake. Norepinephrine enhanced ketogenesis from [1-14C]palmitate in a physiologic range of fatty acid concentrations (0.5-2.5 mM), but failed to affect fatty acid esterification to phospholipids or mono- and diglycerides. In contrast to long-chain fatty acids, oxidation of the medium-chain fatty acid [1-14C]octanoate to ketone bodies was not enhanced by norepinephrine, whereas CO2 production increased. The effect of norepinephrine on [1-14C]fatty acid oxidation was blocked by the alpha 1 receptor blocker prazosin. The results demonstrate that norepinephrine diverts long-chain fatty acids into the pathways of oxidation and ketogenesis away from esterification, suggesting enhanced carnitine-dependent mitochondrial fatty acid uptake. The studies using octanoate indicated that norepinephrine also enhanced fatty acid oxidation by increasing the flux of acetyl-CoA through the Krebs cycle. The data suggest that stress-associated sympathetic activation and norepinephrine discharge, as observed in diabetic ketoacidosis, result in direct activation of ketogenesis in the liver.

Adrenergic alpha-Antagonists↗