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Results for “Norepinephrine”

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PubMed1995

Alpha-adrenoceptor modulation of norepinephrine and ATP release in isolated kidneys of spontaneously hypertensive rats.

The present study investigates sympathetic cotransmission and its alpha-adrenoceptor-mediated modulation in kidneys of spontaneously hypertensive rats (SHR, 12 to 14 weeks) and age-matched normotensive Wistar-Kyoto rats (WKY). In the presence of cocaine and corticosterone, renal nerve stimulation at 1 Hz (30 seconds) induced a greater outflow of norepinephrine in SHR (4.2 +/- 0.2 pmol/g kidney) than in WKY (3.0 +/- 0.2 pmol/g kidney). The alpha 2-adrenoceptor antagonist rauwolscine (0.01 to 1 mumol/L) increased the stimulation-induced norepinephrine outflow to a greater extent in SHR than in WKY. In contrast, the alpha 1-adrenoceptor antagonist prazosin (0.03 to 3 mumol/L) increased the stimulation-induced norepinephrine outflow to a greater extent in WKY than in SHR. This difference was not observed in the presence of the P1-purinoceptor antagonist 8-(p-sulfophenyl)theophylline (100 mumol/L). Stimulation at 4 Hz (30 seconds) induced an outflow of ATP (SHR, 12.7 +/- 3.3 pmol/g kidney; WKY, 16.7 +/- 2.1 pmol/g kidney; perfusion solution without cocaine and corticosterone). Prazosin (0.03 mumol/L) markedly reduced pressor responses to stimulation and inhibited the induced ATP outflow by 60% to 70%. When prazosin (0.03 mumol/L) was present, rauwolscine (0.1 mumol/L) increased the induced outflow of norepinephrine and ATP and markedly enhanced prazosin-resistant pressor responses. These pressor responses were abolished by the P2-purinoceptor antagonist suramin (300 mumol/L). The results demonstrate an increased alpha 2-adrenoceptor-mediated automodulation of norepinephrine release in SHR kidneys caused by increased intrasynaptic norepinephrine levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1996

Angiotensin II increases norepinephrine turnover in the anteroventral third ventricle of spontaneously hypertensive rats.

We evaluated the effect of angiotensin II (Ang II) administered by intracerebroventricular injection on norepinephrine turnover in the anteroventral third ventricle in adult spontaneously hypertensive rats (SHR, n = 35) and age-matched Wistar-Kyoto rats (WKY, n = 38). Ang II (100 ng) or saline (vehicle control) was administered into the cerebral ventricle 30 minutes after injection of alpha-methyl-p-tyrosine (250 mg/kg IP). Norepinephrine turnover was assessed by evaluation of the norepinephrine concentration before and 1 hour after such administration. The pressor response to Ang II administration was significantly greater in SHR than in WKY (+43 +/- 3 versus +23 +/- 2 mm Hg, P < .01). Baseline norepinephrine turnover (response to saline) was reduced in the ventral median preoptic nucleus of SHR. Ang II significantly increased norepinephrine turnover in the organum vasculosum lamina terminalis and ventral median preoptic nucleus of SHR (organum vasculosum lamina terminalis: 40 +/- 5% by Ang II versus 18 +/- 6% by saline, P < .05; ventral median preoptic nucleus: 32 +/- 3% by Ang II versus 21 +/- 2% by saline, P < .05) but not of WKY (37 +/- 5% versus 29 +/- 5%, P = NS, and 30 +/- 2% versus 32 +/- 3%, P = NS, respectively). Thus, norepinephrine turnover in the anteroventral third ventricle region induced by intracerebroventricular administration of Ang II was increased in SHR. This effect may contribute to the enhanced pressor response to central Ang II seen in this model.

Angiotensin II↗

PubMedDate not supplied

Prolonged exposure to ouabain eliminates the greater norepinephrine-dependent calcium sensitivity of resistance vessels in spontaneously hypertensive rats.

The effects of 30 minutes of exposure to ouabain on calcium sensitivity have been investigated in two types of resistance vessels from 12 pairs of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Branches of the superior mesenteric and femoral arteries, with internal diameters of about 200 micrometer, were mounted as ring preparations in a myograph capable of measuring their isometric wall tension. Dose-response curves for calcium upon norepinephrine stimulation were determined under conditions where neuronal uptake was eliminated. Initially, when stimulated with norepinephrine, the SHR vessels from both locations were more sensitive to calcium and had stronger contractions than their controls. The addition of ouabain (1 mM) to the relaxed vessels immediately elicited a moderate, transient contraction in the branches of the femoral artery, whereas no response was observed in the mesenteric vessels. Although the addition of ouabain to activated vessels produced an immediate potentiation of the response, prolonged (30-minute) exposure to ouabain reduced active tension development upon norepinephrine stimulation in all vessels. The reduction was greatest in the SHR vessels, so that, under these conditions, the norepinephrine-activated calcium sensitivity of corresponding SHR and WKY vessels was similar. By contrast, responses to norepinephrine in high potassium solution were unaffected. The results suggest that under normal conditions, SHR vessels may have a specific increase in the permeability of the norepinephrine-activated calcium channels. Prolonged exposure to ouabain appears to reduce the permeability of these channels, providing an explanation for why this treatment eliminates the difference in calcium sensitivity of the SHR and WKY vessels.

Animals↗

PubMedDate not supplied

Increased plasma norepinephrine accompanies persistent tachycardia after hydralazine.

To determine the role of the peripheral sympathetic nervous system in the persistent tachycardia caused by the antihypertensive drug hydralazine, we examined the temporal relationships between the changes in heart rate and plasma norepinephrine concentration and the reduction in blood pressure produced by a range of doses of hydralazine administered intravenously to five hypertensive patients. Significant linear correlations were found between the increases in heart rate and plasma norepinephrine concentration and the reduction in blood pressure at 15 and 30 minutes after injection. However, at 240 minutes after injection, changes in heart rate and plasma norepinephrine were not correlated with changes in blood pressure and were disproportionately elevated relative to the reduction in blood pressure. A significant linear correlation between changes in heart rate and plasma norepinephrine concentration was noted at 15, 30, and 240 minutes after injection. The temporal discordance of the changes of both heart rate and plasma norepinephrine relative to the reduction in blood pressure and the significant linear correlation between the increases in heart rate and plasma norepinephrine concentration suggest that continued activation of the peripheral sympathetic nervous system contributes to the persistent tachycardia seen after the administration of hydralazine.

Blood Pressure↗

PubMedDate not supplied

Norepinephrine-induced potentiation of arginine vasopressin reactivity in arterioles of the spontaneously hypertensive rat.

We have studied microvascular reactivity to vasopressin alone and in combination with norepinephrine in young (6- to 8-week-old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) controls. Closed-circuit TV microscopy was used to quantify the in vivo diameter responses of small arterioles (17 to 26 mu) to vasopressin (1.25 X 10(-8) to 3.75 X 10(-7) M) injected intraarterially alone and with simultaneous topical suffusion of a subthreshold concentration of norepinephrine in the cremaster muscle microcirculation. Percent decrease in luminal diameter was integrated over a 30-second period to obtain log concentration response curves. The vasoconstrictor response to vasopressin was concentration-dependent in both groups (p less than 0.001). A significant increase in reactivity to vasopressin alone was exhibited by the SHR arterioles compared to the WKY vessels (p less than 0.02). Maximum constriction was 55% higher in the SHR (p less than 0.04). The SHR also demonstrated a greater sensitivity to vasopressin (p less than 0.02). Vasopressin-induced vasoconstriction was potentiated by norepinephrine in the SHR, demonstrated by the significant shift of the curve up and to the left of the SHR response curve to vasopressin alone (p less than 0.01). The maximum response was 38% greater (p less than 0.02). Sensitivity was significantly enhanced (p less than 0.01). Additionally, the presence of norepinephrine stimulated a three-fold greater incidence of complete closure. In contrast to SHR results, topical suffusion of norepinephrine did not significantly alter the reactivity of the WKY arterioles to vasopressin-induced constriction. Our results support a role for vasopressin as a potential vasoconstrictor in the developing stage of SHR hypertension which may be modulated by norepinephrine and thus contribute to the elevated total peripheral resistance observed.

Administration, Topical↗

PubMedDate not supplied

Reactivity to norepinephrine and effect of sodium on blood pressure during weight loss.

Eighteen moderately obese middle-aged men with untreated mild hypertension were randomized to two groups and placed on a low energy diet regimen for 9 to 11 weeks. In Group I (n = 10) the amount of sodium chloride in the diet maintained the urinary sodium excretion at the predieting level. Mean body mass was reduced by 9.1 +/- 0.7 (SEM) kg. Mean intra-arterial pressure showed no significant change. There were significant decreases in heart rate (p less than 0.05) and urinary norepinephrine excretion (p less than 0.05) but not in plasma concentration of norepinephrine. In Group II (n = 8) energy as well as sodium intake was restricted, with a 95 +/- 22 mmol/24 hour reduction of urinary sodium excretion. Body mass decreased by 9.3 +/- 1.1 kg, and mean arterial pressure decreased by -18.9 to -4.3 mm Hg (95% confidence interval). There were also significant reductions in heart rate (p less than 0.001) and plasma norepinephrine concentrations (p less than 0.01) but not in urinary norepinephrine excretion. The pressor response (mean arterial pressure) to norepinephrine infusion at different dose rates was significantly elevated (p less than 0.05) in Group I during dieting in comparison with baseline. The blood pressure response to norepinephrine during dieting in patients in Group II was not changed from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

PubMed1978

Increased renal vascular reactivity to angiotensin II but not to nerve stimulation or exogenous norepinephrine in renal hypertensive rats.

We isolated and perfused both the "clipped" and "contralateral" kidneys from Goldblatt renal hypertensive and sham-operated control rats, 1--104 days postoperatively. Responses to renal nerve stimulation were depressed in clipped kidneys from hypertensive rats (1 day postoperative), and these kidneys were supersensitive to exogenous norepinephrine (1--31 day) when compared with the contralateral organ of the same animal. Similar alterations were found between clipped and contralateral kidneys from sham-operated control rats. There was no difference in responses to renal nerve stimulation of norepinephrine between clipped kidneys from hypertensive and control rats, but clipped kidneys from hypertensive rats were supersensitive to angiotensin II (17 and 31 days). Comparison of contralateral kidneys from hypertensive and control rats revealed no change in norepinephrine sensitivity or in responses to renal nerve stimulation, but there was a reduction in the slope of the dose-response curve to norepinephrine and of the maximal effect of the catecholamine (104 days) and a pronounced supersensitivity to angiotensin II (17--104 days) in the hypertensive rats. These results indicate that (1) renal nerve function and norepinephrine sensitivity of the isolated renal vasculature are unchanged in renal hypertension, but clipping partially denervates the kidney causing depressed nerve function and unilateral norepinephrine supersensitivity, unrelated to hypertension; (2) the prolonged high pressure load on the contralateral kidney may impair the function of the vascular smooth muscle; and (3) bilateral supersensitivity to angiotensin II is associated with hypertension but is not solely a consequence of the high pressure.

Angiotensin II↗

PubMed1982

The release of endogenous norepinephrine from the coccygeal artery of spontaneously hypertensive and Wistar-Kyoto rats.

The potassium (K+)-induced release of endogenous norepinephrine from the coccygeal artery of spontaneously hypertensive rats has been studied as a function of the development of hypertension. The absolute amount of norepinephrine released by potassium was greater in spontaneously hypertensive rat than the normotensive Wistar-Kyoto rat, regardless of age or blood pressure. However, the %-fractional release was elevated only in the rats with chronic hypertension. Preincubation of tissues with the alpha 2-antagonist, yohimbine, significantly enhanced norepinephrine overflow in all tissues studied. Young hypertensive animals demonstrated an enhancement equal to the Wistar-Kyoto rat controls. In the adult spontaneously hypertensive rat, however, there was a significantly lesser enhancement produced by yohimbine. Levels of norepinephrine in the nerves supplying the artery were greater in the prehypertensive spontaneously hypertensive rat than the age-matched Wistar-Kyoto rat. The norepinephrine content in arteries from adult animals was equivalent. The explanation for the attenuation of the yohimbine effect of chronic hypertensive animals is unclear. Although several explanations are possible, the data are consistent with the hypothesis that spontaneously hypertensive rats with chronic hypertension have subsensitive prejunctional alpha 2-receptors as evidenced by an increased %-fractional release of norepinephrine and a decreased enhancement of overflow in the presence of yohimbine. Clearly, further studies are needed to answer this provocative question and to understand the complex interactions of adrenergic neurotransmission in hypertensive animals.

Animals↗

PubMed1983

Prejunctional and postjunctional actions of endogenous norepinephrine at the sympathetic neuroeffector junction in canine coronary arteries.

The effects of endogenous and of exogenous norepinephrine were studied in isolated rings of canine left circumflex coronary artery and its first ventricular branch. Norepinephrine was released from adrenergic nerve endings by transmural electrical stimulation and by tyramine. In rings contracted with prostaglandin F2 alpha, transmural electrical stimulation resulted in frequency-dependent relaxations which were blocked by propranolol or tetrodotoxin; tyramine and exogenous norepinephrine caused concentration-dependent relaxations which were blocked by propranolol. The tyramine-induced relaxations also were inhibited by cocaine. The left circumflex artery was less sensitive than its branch to beta-adrenergic activation; this difference was significant even between rings of the two vessels immediately adjacent to the branching point and was abolished by phentolamine. In the presence of propranolol, transmural electrical stimulation, tyramine and phenylephrine, produced contractions of the left circumflex artery, but not the branch; these contractions were prevented by phentolamine. Phentolamine, but not prazosin, augmented the beta-adrenergic response of left circumflex artery to low frequency stimulation; in arteries preincubated with 3H-norepinephrine, this was accompanied by an increased overflow of tritiated neurotransmitter. The prejunctional effect of phentolamine was also evident in branch coronary arteries which exhibit no postjunctional alpha-adrenergic responses. With high frequency stimulation, both alpha-adrenergic antagonists equally augmented the relaxation of left circumflex artery; the efflux of tritiated norepinephrine was not different from untreated arteries. These experiments demonstrate, in isolated coronary arteries, that the primary adrenergic response to released endogenous norepinephrine is beta-adrenergic relaxation. The prejunctional effects of nonspecific alpha-adrenergic antagonists preclude their use in determining the importance of postjunctional coronary alpha-adrenergic receptor activation caused by sympathetic nerve stimulation.

Adrenergic alpha-Antagonists↗

PubMed1990

Failure of the cholinergic modulation of norepinephrine release during acute myocardial ischemia in the rat.

The effect of ischemia on cholinergic presynaptic inhibition of exocytotic norepinephrine release was studied in the innervated perfused rat heart. In normoxic hearts, vagal nerve stimulation significantly reduced exocytotic norepinephrine overflow to 75% of control values. This inhibitory effect was not affected by 3 minutes of low-flow ischemia (67% of control overflow values), but was attenuated or abolished by 10-minute low-flow ischemia or by 1-, 3-, and 5-minute stop-flow ischemia (107%, 85%, 101%, and 120% of control overflow values, respectively). The alpha-adrenergic antagonist phentolamine could completely or partly restore the failure of vagally induced inhibition of norepinephrine overflow in hearts with 1-, 3-, and 5-minute stop-flow ischemia (72%, 73%, and 85% of control overflow values, respectively). The muscarinic agonist methacholine substantially inhibited norepinephrine overflow to 18% of control overflow values in normoxic hearts. This effect was also significantly attenuated by 10-minute low-flow ischemia or by 1-, 3-, and 5-minute stop-flow ischemia (46%, 38%, 53%, and 55% of control overflow values, respectively). The cholinesterase inhibitor physostigmine did not restore the methacholine-induced inhibition of norepinephrine overflow after 3-minute stop-flow ischemia to normoxic level (55% vs. 17%). These results indicate that myocardial ischemia interferes with endogenous and exogenous cholinergic presynaptic inhibition of norepinephrine overflow in the rat heart. The extent of this attenuation depends on the severity and duration of ischemia. Reduced exocytotic acetylcholine release, which is at least in part due to an enhanced adrenergic presynaptic modulation, and dysfunction of presynaptic muscarinic receptors are suggested as two possible mechanisms.

Animals↗

PubMed1992

Sympathetic stimulation and norepinephrine infusion modulate extracellular potassium concentration during acute myocardial ischemia.

The purpose of this study was to investigate whether sympathetic stimulation modulated the rise in extracellular K+ concentration ([K+]o) evoked by acute myocardial ischemia. In 35 alpha-chloralose-anesthetized dogs, we measured changes in [K+]o during acute myocardial ischemia in the presence and absence of sympathetic stimulation or norepinephrine infusion. A series of four 5-minute occlusions of the distal left anterior descending coronary artery (LAD) was completed in 18 dogs. Thirty minutes of reperfusion separated each LAD occlusion. Four to five K(+)-sensitive electrodes were inserted into the left ventricular midmyocardium that was perfused by the distal LAD. Lead II of the electrocardiogram, arterial pressure, and [K+]o were recorded, and the right atrium was paced at a constant cycle length. The first, second, and fourth LAD occlusions were done in the absence of sympathetic stimulation or norepinephrine infusion. The changes in [K+]o evoked by the first LAD occlusion differed (p < 0.05) from those elicited by the second and fourth occlusions. However, the changes in [K+]o during the second and fourth LAD occlusions were similar (p > 0.2) and served as controls for the responses obtained during the third occlusion. Two minutes before the third LAD occlusion, sympathetic stimulation (4 Hz) or norepinephrine infusion (0.25-0.5 micrograms/kg per minute i.v.) was begun and was continued until 2 minutes after reperfusion. We found that sympathetic stimulation and norepinephrine infusion increased (p < 0.05) myocardial blood flow in both normal and ischemic tissue. The mean response recorded by 23 K(+)-sensitive electrodes in 11 dogs showed that sympathetic stimulation increased (p < 0.001) the [K+]o at 1, 2, 3, 4, and 5 minutes after the onset of LAD occlusion compared with the second and fourth occlusions. In contrast, the mean response recorded by 20 K(+)-sensitive electrodes in seven dogs showed that norepinephrine infusion reduced (p < 0.02) the [K+]o at 4 and 5 minutes after the onset of LAD occlusion. These data show that sympathetic stimulation increased the [K+]o evoked by acute myocardial ischemia, an effect that was not mimicked by the intravenous administration of norepinephrine.

Animals↗

PubMed1994

Altered pulmonary microvascular reactivity to norepinephrine in canine pacing-induced heart failure.

Pulmonary hypertension in congestive heart failure causes medial hypertrophy in pulmonary vessels and thickening of the endothelial basement membrane. In this study, the functional consequences of such pulmonary vascular adaptations were evaluated. Heart failure was induced in dogs by rapid ventricular pacing (240 beats per minute) for 28 days, at which time left ventricular shortening fraction was decreased by 57% compared with that at baseline. Lung lobes from paced (n = 56) and control dogs (n = 68) were isolated and perfused with autologous blood. Total, arterial (Ra), and venous (Rv) vascular resistances were significantly increased and vascular capacitance decreased in lobes from paced animals compared with controls. Increments in Ra and Rv after intra-arterial boluses of norepinephrine were measured before and after sequential addition of the alpha 1- and alpha 2-receptor antagonists prazosin (16 mumol/L) and yohimbine (0.1 mumol/L) in the presence or absence of propranolol (5 mumol/L). Norepinephrine (1 to 40 micrograms) had little effect on Ra in the absence of propranolol, a pattern that persisted in control lobes after propranolol. However, when lobes from paced animals were pretreated with propranolol, norepinephrine increased Ra, Rv was increased after norepinephrine in control lobes, an effect that was enhanced in the paced group. In both groups, the increment in Rv was greater after propranolol. Irrespective of propranolol pretreatment, prazosin significantly attenuated, if not abolished, the response to norepinephrine. The enhancement in venous vascular reactivity in lobes from paced animals remained when venous pressure was elevated to 20 cm H2O. In control lobes under conditions of elevated tone or when endothelium-dependent relaxing factor was blocked, responses to norepinephrine did not mimic those observed in the paced group. Microvascular permeability, as measured by the capillary filtration coefficient, was not altered in the paced group. We conclude that the pulmonary adaptations to 4 weeks of rapid ventricular pacing include functional changes in pulmonary hemodynamics and vascular reactivity but not in microvascular permeability.

Adrenergic beta-Antagonists↗

PubMed1997

Bradykinin B2-receptor activation augments norepinephrine exocytosis from cardiac sympathetic nerve endings. Mediation by autocrine/paracrine mechanisms.

We determined whether local bradykinin production modulates cardiac adrenergic activity. Depolarization of guinea pig heart sympathetic nerve endings (synaptosomes) with 1 to 100 mmol/L K+ caused the release of endogenous norepinephrine (10% to 50% above basal level). This release was exocytotic, because it depended on extracellular Ca2+, was inhibited by the N-type Ca(2+)-channel blocker omega-conotoxin and the protein kinase C inhibitor Ro31-8220, and was potentiated by the neuronal uptake-1 inhibitor desipramine. Typical of adrenergic terminals, norepinephrine exocytosis was enhanced by activation of prejunctional angiotensin AT1-receptors and attenuated by adrenergic alpha 2-receptors, adenosine A1-receptors, and histamine H3-receptors. Exogenous bradykinin enhanced norepinephrine exocytosis by 7% to 35% (EC50, 17 nmol/L), without inhibiting uptake 1. B2-receptor, but not B1-receptor, blockade antagonized this effect. The kininase II/angiotensin-converting enzyme inhibitor enalaprilat and the addition of kininogen or kallikrein enhanced norepinephrine exocytosis by approximately equal to 6% to 40% (EC50, 20 nmol/L) and approximately equal to 25% to 60%, respectively. This potentiation was prevented by serine protease inhibitors and was antagonized by B2-receptor blockade. Therefore, norepinephrine exocytosis is augmented when bradykinin synthesis is increased or when its breakdown is inhibited. This is the first report of a local kallikrein-kinin system in adrenergic nerve endings capable of generating enough bradykinin to activate B2-receptors in an autocrine/paracrine fashion and thus enhance norepinephrine exocytosis. This amplification process may operate in disease states, such as myocardial ischemia, associated with severalfold increases in local kinin concentrations.

Animals↗

PubMed1977

Norepinephrine and 3-methoxy-4-hydroxyphenyl glycol gradients in human cerebrospinal fluid.

The presence of abnormal levels of 3-methoxy-4-hydroxyphenyl glycol (MHPG) in the cerebrospinal fluid (CSF) of some patients with affective disorders may indicate abnormal norepinephrine metabolism in these patients. The authors evaluated the relationship between norepinephrine and MHPG in CSF and found that both are present in increasing levels as more CSF is removed from the lumbar puncture needle. Norepinephrine and MHPG are closely related, although norepinephrine levels are more variable within and between subjects. Both norepinephrine and MHPG levels in CSF should provide important information about norepinephrine metabolism in affective disorders.

Affective Symptoms↗

PubMed1997

Effects of Alzheimer's disease severity on cerebrospinal fluid norepinephrine concentration.

OBJECTIVE: Although loss of noradrenergic neurons in the locus ceruleus has been consistently demonstrated postmortem in Alzheimer's disease, several small studies suggest that indices of central noradrenergic activity increase with the severity of Alzheimer's disease in living patients. The authors estimated the effect of Alzheimer's disease severity on central noradrenergic activity by comparing the CSF norepinephrine concentrations of subjects with Alzheimer's disease in earlier and advanced stages. The effect of normal aging on CSF norepinephrine also was determined. METHOD: Lumbar punctures were performed in 49 subjects with Alzheimer's disease of mild or moderate severity, 25 subjects with advanced Alzheimer's disease, 42 normal older subjects, and 54 normal young subjects. Advanced Alzheimer's disease was defined prospectively by a Mini-Mental State score of less than 12. Norepinephrine was measured by radioenzymatic assay. RESULTS: CSF norepinephrine concentration was significantly higher in the patients with advanced Alzheimer's disease (mean = 279 pg/ml, SD = 122) than in those with mild to moderate severity (mean = 198 pg/ml, SD = 89), normal older subjects (mean = 219 pg/ml, SD = 88), or normal young subjects (mean = 154 pg/ml, SD = 53). CSF and plasma norepinephrine levels and mean arterial blood pressure all were higher in the older subjects than in the young subjects. CONCLUSIONS: Despite the loss of locus ceruleus neurons in Alzheimer's disease, the aging-associated high concentration of CSF norepinephrine is retained in the earlier stages of Alzheimer's disease and increases further as the disease progresses. Increased brain noradrenergic activity may contribute to the agitated behaviors or cognitive deficits of patients with advanced Alzheimer's disease.

Adult↗

PubMed2001

CSF norepinephrine concentrations in posttraumatic stress disorder.

OBJECTIVE: Despite evidence of hyperresponsive peripheral and central nervous system (CNS) noradrenergic activity in posttraumatic stress disorder (PTSD), direct measures of CNS norepinephrine in PTSD have been lacking. The goal of this study was to determine serial CSF norepinephrine levels in patients with PTSD. METHOD: CSF samples were obtained serially over a 6-hour period in 11 male combat veterans with chronic PTSD and eight healthy men through an indwelling subarachnoid catheter. Thus the authors were able to determine hourly CSF norepinephrine concentrations under baseline (unstressed) conditions. Severity of the patients' PTSD symptoms was assessed with the Clinician-Administered PTSD Scale. RESULTS: CSF norepinephrine concentrations were significantly higher in the men with PTSD than in the healthy men. Moreover, CSF norepinephrine levels strongly and positively correlated with the severity of PTSD symptoms. Plasma norepinephrine concentrations showed no significant relationship with the severity of PTSD symptoms. CONCLUSIONS: These findings reveal the presence of greater CNS noradrenergic activity under baseline conditions in patients with chronic PTSD than in healthy subjects and directly link this pathophysiologic observation with the severity of the clinical posttraumatic stress syndrome.

Adult↗

PubMed1998

Heparin attenuates norepinephrine-induced venoconstriction.

Reversal by heparin of norepinephrine-induced constriction of normal hand veins was studied. Venous size was measured using a linear variable differential transformer (LVDT) during infusions of saline, norepinephrine, insulin and norepinephrine, and graded doses of heparin with norepinephrine. Heparin reduced the venoconstrictive effects of norepinephrine (p < 0.01), with the effects beginning at 18.5 nmol/min (0.05 U/min) and reaching a maximum between 185 nmol/min and 1.85 mumol/min (0.5 and 5 U/min). Maximal heparin-induced venorelaxation correlated with the maximal insulin effect within individuals (r = 0.8, p < 0.01) and was unchanged by the addition of insulin. Methylene blue, a non-specific inhibitor of the nitric oxide cGMP cascade, reduced heparin-induced venorelaxation. In conclusion, heparin in either physiologic or pharmacologic concentration attenuated norepinephrine-induced venoconstriction. A common mechanism of venorelaxation by heparin and insulin is not excluded given the correlation and lack of additivity of maximum effects and their inhibition by methylene blue.

Adult↗

PubMed2006

Dopexamine and norepinephrine versus epinephrine on gastric perfusion in patients with septic shock: a randomized study [NCT00134212].

INTRODUCTION: Microcirculatory blood flow, and notably gut perfusion, is important in the development of multiple organ failure in septic shock. We compared the effects of dopexamine and norepinephrine (noradrenaline) with those of epinephrine (adrenaline) on gastric mucosal blood flow (GMBF) in patients with septic shock. The effects of these drugs on oxidative stress were also assessed. METHODS: This was a prospective randomized study performed in a surgical intensive care unit among adults fulfilling usual criteria for septic shock. Systemic and pulmonary hemodynamics, GMBF (laser-Doppler) and malondialdehyde were assessed just before catecholamine infusion (T0), as soon as mean arterial pressure (MAP) reached 70 to 80 mmHg (T1), and 2 hours (T2) and 6 hours (T3) after T1. Drugs were titrated from 0.2 microg kg(-1) min(-1) with 0.2 microg kg(-1) min(-1) increments every 3 minutes for epinephrine and norepinephrine, and from 0.5 microg kg(-1) min(-1) with 0.5 microg kg(-1) min(-1) increments every 3 minutes for dopexamine. RESULTS: Twenty-two patients were included (10 receiving epinephrine, 12 receiving dopexamine-norepinephrine). There was no significant difference between groups on MAP at T0, T1, T2, and T3. Heart rate and cardiac output increased significantly more with epinephrine than with dopexamine-norepinephrine, whereas. GMBF increased significantly more with dopexamine-norepinephrine than with epinephrine between T1 and T3 (median values 106, 137, 133, and 165 versus 76, 91, 90, and 125 units of relative flux at T0, T1, T2 and T3, respectively). Malondialdehyde similarly increased in both groups between T1 and T3. CONCLUSION: In septic shock, at doses that induced the same effect on MAP, dopexamine-norepinephrine enhanced GMBF more than epinephrine did. No difference was observed on oxidative stress.

Aged↗