Higher Norepinephrine Research Articles

Absence of vasospasm in radial artery CABG on high-dose norepinephrine

One of the concerns in using radial artery as coronary artery bypass grafts centers around its unusual propensity for vasospasm when experimentally exposed to norepinephrine. This case report demonstrates an absence of vasospasm in a radial artery graft on high dose norepinephrine and may provide reassurance when α-agonists are required in this setting.

Plasma norepinephrine and prediction of outcome in major depressive disorder

Background: Several epidemiologic and clinical factors have been shown to predict long term outcome in major depressive disorder (MDD). The value of biological predictors has not been extensively studied. This study examined whether plasma norepinephrine may be useful in predicting outcome in MDD. Methods: Forty patients were followed up 8 years after an index major depressive episode. Three outcome variables were assessed: time to first recurrence (the primary outcome measure), the Lee and Murray criteria and the Depression Outcome Scale (DOS). The results were examined against plasma norepinephrine value, at the index episode, using survival analysis and linear regression. Results: High plasma norepinephrine at the index episode was positively and significantly associated with time to first recurrence for patients with nonpsychotic MDD ( n = 31, χ 2 = 8.38, on 1 df, p < .01). Similarly, plasma norepinephrine was significantly associated with good global outcome, both using Lee and Murray criteria ( n = 34, adjusted R 2 = .24, p < .01) and DOS criteria ( n = 31, adjusted R 2 = .17, p < .01) for this group of patients. In contrast, plasma norepinephrine was not significantly related to outcome for MDD with psychotic features. Conclusions: Plasma norepinephrine at index episode seems to be a predictor of outcome in MDD.

Patterns of cerebrospinal fluid catechols support increased central noradrenergic responsiveness in aging and Alzheimer’s disease

Background: High cerebrospinal fluid (CSF) norepinephrine (NE) concentrations in aging and Alzheimer’s disease (AD) could reflect decreased NE clearance from central nervous system (CNS) extracellular fluid or increased release of NE into CNS extracellular fluid. Measuring CSF concentrations of the intraneuronal NE metabolite dihydroxyphenylglycol (DHPG), an estimate of NE clearance, and the NE precursor dihydroxyphenylacetic acid (DOPA), an estimate of NE biosynthesis, can help differentiate these mechanisms. Methods: NE, DHPG, and DOPA were determined by HPLC in CSF and plasma obtained following yohimbine, clonidine, and placebo. Ten AD, 10 older, and 11 young subjects were studied. Results: CSF DOPA following yohimbine was higher in older and AD than in young subjects. CSF DHPG did not differ among groups. Plasma DOPA following yohimbine was higher in AD than in young subjects. Conclusions: During alpha-2 adrenoreceptor blockade in both aging and AD, there are increased responses of CNS NE biosynthesis and release with unchanged CNS NE clearance. This pattern is consistent with partial loss of CNS noradrenergic neurons with compensatory activation of remaining CNS noradrenergic neurons. Given the marked loss of locus coeruleus (LC) noradrenergic neurons in AD, achievement of high CSF NE suggests particularly prominent compensatory activation of remaining LC neurons in this disorder.

The role of ascending neuronal pathways in stress-induced release of noradrenaline in the hypothalamic paraventricular nucleus of rats.

Central catecholaminergic pathways carrying pain-related signals to the hypothalamic paraventricular nucleus (PVN) were investigated in laboratory rats. Four per cent formalin injected subcutaneously was employed as a stressful stimulus. Neuronal activity in brainstem catecholaminergic and paraventricular neurones was assessed by Fos immunohistochemistry. Stress-induced noradrenaline (NE) release from nerve terminals in the PVN was measured in extracellular fluid by in-vivo microdialysis. Within 30 min, formalin elicited a four- to sixfold increase in plasma ACTH and corticosterone concentrations and intense Fos-like activity was seen in the superficial zones of the lumbar spinal cord ipsilateral to the side of the formalin injection. In brainstem catecholaminergic neurones, the PVN, and midline thalamic nuclei, formalin-induced Fos-immunopositivity was equally present in the ipsi- and contralateral sides of the injection. An immediate elevation (4-5 times higher than baseline levels) of NE levels was measured in both the right and left PVN after a formalin injection into the right paw. Unilateral surgical transections at the medulla-spinal cord junction failed to affect formalin-induced elevations in NE levels in the PVN independently of the side of the formalin injection or the knife cut. Thus, this observation clearly shows that fibres carrying pain-evoked signals ascend bilaterally from the spinal cord to the brainstem and forebrain. Hemisections of the medulla oblongata between the level of A1-A2 NE cell groups and the locus coeruleus reduced but did not eliminate formalin-induced NE release from the PVN ipsilateral to the knife cut. This effect was independent of the side of the formalin injection. In the contralateral PVN, high and similar NE levels were measured in response to a formalin injection into the right or the left leg. The present study indicates that formalin-induced pain signals are carried by sensory fibres to the ipsilateral spinal cord. From there, axons of different dorsal horn neurones reach noradrenergic cells on both sides of the medulla oblongata. The majority of noradrenergic fibers ascend on the same side and innervate the ipsilateral PVN. Since formalin administration resulted in a moderate elevation of NE levels in the PVN on the operated side, the role of other ascending noradrenergic (from the locus coeruleus) or noncatecholaminergic fibres that could modulate NE release from the PVN should be considered.

EFFECT OF CATECHOLAMINES ON PHOSPHOLIPASE A2 ACTIVITY

S379 INTRODUCTION: Epinephrine (EPI), Norepinephrine (NE) and Dopamine (DA) are commonly used drugs in critical care. While they have well understood pharmacodynamic effects, little is known about the anti- or proinflammatory effect of these substances. Purpose of the study was to establish the anti- or proinflammatory effect of these substances as assessed by the respective effects on PLA2 activity in an in vitro model and to determine the type of activation or inhibition [competitive, un-competitive or noncompetitive (mixed)]. METHODS: 1.) PLA2 (human platelets) was incubated with TRIS-buffer (native) or 1, 10 and 100[micro sign]g of the drugs respectively. PLA2-activity was measured in a radioactive asssay. All values were expressed in % of baseline (BL) values (native activity = 100%). Data were analysed with the Mann-Whitney rank order test. 2.) PLA (2) (porcine) was incubated with different phosphatidyl-choline concentrations and 100[micro sign]g of each drug respectively. Subsequently activity was measured. Lineweaver-Burk representation was used to determine the type of activation/inhibition. RESULTS: (Table 1 and Figure 1)Table 1Figure 1DISCUSSION: High dose EPI, NE and DA activate PLA2. The PLA2 activating effect of the catecholamines while in concordance with the literature was here quantified. The interaction is mixed [enzyme-substrate-activator (ESA) and enzyme-activator (EA) complex formation]. For EPI, NE and DA the physiologic plasma concentrations are in the nmol/l range, while the K values are in the mmol/l range; as such a regulatory function on PLA2 activity can be excluded. Even when ultra high dose iv catecholamine therapy is used, the effect on PLA2 is of no clinical relevance.

Mechanism of Peripheral Noradrenergic Stimulation by Clozapine

Elevated plasma norepinephrine (NE) levels is a relatively consistent clinical effect of clozapine. Plasma NE levels reflect an interplay of release, reuptake, metabolism, and excretion. To explore the mechanism of clozapine-induced plasma NE elevation, we measured arterial plasma levels of NE and other catechols during intravenous infusion of tritium-labeled NE (3H-NE) in schizophrenic patients treated with clozapine, fluphenazine, or placebo. Clozapine-treated patients had markedly higher levels of NE than did the patients treated with fluphenazine or placebo. NE spillover averaged more than three times higher in clozapine-treated patients; whereas NE clearance did not differ among the groups. Production of 3H-dihydroxyphenylglycol (3H-DHPG), a purely intraneuronal metabolite of 3H-NE in clozapine-treated patients was normal, indicating that clozapine did not affect neuronal uptake of NE. Because plasma levels of DHPG and dihydroxyphenylacetic acid (DOPAC), deaminated metabolites of catecholamines, in clozapine-treated patients were normal, clozapine also did not seem to inhibit intraneuronal monoamine oxidase (MAO). High plasma NE levels in clozapine-treated patients, therefore, resulted from increased NE spillover rather than decreased reuptake, metabolism, or clearance.

Pituitary reactivity, androgens and catecholamines in obstructive sleep apnoea. Effects of continuous positive airway pressure treatment (CPAP)

We studied the effects of chronic nocturnal hypoxaemia due to obstructive sleep apnoea syndrome (OSAS) on the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-testicular axes and on catecholamine and cortisol secretion. We investigated whether hormones other than catecholamines may serve as markers for chronic hypoxic stress and the possible effects of nasal continuous positive airway pressure (nCPAP) treatment on endocrine status. Nocturnal oximetry was performed in 16 male patients with OSAS diagnosed by polysomnography, immediately before nCPAP treatment and in 11 of the patients the oximetry was repeated after 7 months of nCPAP therapy. Plasma and urinary catecholamines, luteinizing hormone (LH), testosterone, cortisol, thyroid stimulating hormone (TSH), prolactin (PRL), and the response of TSH and PRL to a thyroid releasing hormone (TRH) challenge test were measured immediately before and after 7 months of nCPAP treatment. Subnormal LH and TSH and elevated serum cortisol as well as increased nocturnal urinary norepinephrine levels were found in patients prior to treatment; otherwise endocrine values were normal. There was a significant correlation between low pretreatment nocturnal arterial oxygen saturation and high plasma and urinary norepinephrine levels. The nCPAP treatment caused significant reduction in serum prolactin and TSH, and significant reduction in plasma epinephrine and urinary norepinephrine. The reduction in serum TSH and urinary norepinephrine was most pronounced in the subjects with the worst pretreatment nocturnal hypoxaemia. No other significant changes were found in basal hormone levels. The response to TRH challenge was normal before and after treatment and was not influenced by CPAP therapy. OSAS is associated with elevated catecholamine and cortisol and decreased TSH and LH levels but a normal response to TRH challenge and a normal androgen status. Apart from catecholamines, none of the hormones studied is likely to serve as a specific marker for chronic hypoxic stress.

Blood Pressure and Vasoactive Hormones in Mild Preeclampsia and Normal Pregnancy

Objective: Changes in vasoactive hormones are reported to play an important role in the pathogenesis of preeclampsia linking placental hypoperfusion with hypertension, systemic disease, and proteinuria. We, therefore, studied diurnal patterns of vasoactive hormones in mild preeclampsia.Methods: Venous blood samples were drawn every 2 h over 25 h for measurements of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine, renin activity, and aldosterone and two urine collections (12 h each) for stable prostaglandin metabolite measurements. The patients were nine women with mild preeclampsia and, for comparison, nine control women matched for gestation and parity.Results: Women with mild preeclampsia had higher norepinephrine levels throughout 25 h, and lower systemic prostacyclin production as measured by the urinary 2,3-dinor-6-keto PGF1α excretion during the daytime. Plasma endothelin and ANP and BNP concentrations tended to be higher throughout 25 h in preeclampsia, but differences between the two groups did not reach levels of statistical significance. Plasma renin activity and aldosterone did not differ between the groups. Whereas control women exhibited a diurnal variation in plasma norepinephrine, ANP, BNP, and aldosterone, and in both urinary prostacyclin and thromboxane A2 metabolites, this was less distinct or absent in patients with mild preeclampsia.Conclusions: We conclude that mild preeclampsia is associated with elevated plasma norepinephrine levels, lower systemic daytime production of prostacyclin, and blunting of the normal diurnal variation for a number of indices including plasma levels of BNP, ANP, norepinephrine, and aldosterone, and urinary prostacyclin metabolites.

Magnesium dynamics and sympathetic nervous system activity in patients with chronic heart failure.

This study was undertaken in patients with heart failure to investigate the relation between plasma norepinephrine (NE) concentration and Mg dynamics. The study subjects comprised 16 patients with chronic heart failure (mean age 64.9+/-10.0 years). Cardiopulmonary exercise testing was performed on all patients, and anaerobic threshold (AT), peak oxygen uptake (peak VO2) and peak exercise time were measured. Resting and peak values of plasma NE concentration and serum and erythrocyte magnesium concentration were also measured. The results were as follows: the serum Mg concentration was increased significantly immediately after exercise (p<0.01), and the erythrocyte Mg concentration showed a tendency to decrease (p<0.1). The resting plasma NE level was inversely correlated with AT (p<0.05, r=-0.57), peak VO2 (p<0.05, r=-0.55) and peak exercise time (p<0.01, r=-0.62). When the plasma NE concentration at rest was analyzed in 2 groups of patients, ie, those with higher than average and those with lower than average concentrations, the resting erythrocyte Mg concentration was significantly lower in the high-NE group (2.2+/-0.3 mg/dl) than in the low-NE group (2.7+/-0.5 mg/dl) (p<0.05). The data indicate that patients with chronic heart failure associated with high NE levels at rest who showed low exercise tolerance have intracellular hypomagnesemia, which may be caused by Mg migration from intracellular to extracellular spaces.

A proposed role for nerve growth factor in the etiology of multiple sclerosis

It is proposed that, in addition to genetic factors involved in immune attack on myelin, higher concentrations of nerve growth factor in certain tissues during development determine susceptibility to multiple sclerosis. High early nerve growth factor in some vasculature of spontaneously hypertensive rats increases sympathetic innervation and catecholamine production in these vessels. They become more sensitive than controls to noradrenaline after chemical sympathectomy. Continued exposure to high noradrenaline can result in sympathectomy-like effects, heightening sensitivity to constricting neurotransmitters. Vasoresponses of spontaneously hypertensive rats are impaired with submaximal but not maximal hypoxia. Such a situation in multiple sclerosis patients could result in insufficient blood flow by vasoconstriction until it becomes maximal. Glutamate increase by ischemia and hyperemic release of free radicals could injure neurons, prompting an immune response to myelin proteins in susceptible people. Developmental adaptation to situations requiring lower sympathetic activity might help counteract these effects.

Migration of dominant pacemaker region in rat sinoatrial node

The location of dominant pacemaker region in isolated rat sinoatrial node in the presence of different concentrations of norepinephrine is determined by intracellular recording of action potential. A linear relationship is revealed between the concentration of norepinephrine and the shift of pacemaker zone along the node axis within physiological concentrations of the transmitter. At high concentrations norepinephrine affects primarily the parameters of action potential in pacemaker cells.

Relation of blood volume and blood pressure in orthostatic intolerance.

A complex but crucial relationship exists between blood volume and blood pressure in human subjects; it has been recognized that in essential hypertension, renovascular hypertension, and pheochromocytoma, the relationship between plasma volume and diastolic blood pressure is an inverse one. This phenomenon has not been studied in individuals with low normal and reduced blood pressures. Orthostatic intolerance is a commonly encountered abnormality in blood pressure regulation often associated with tachycardia in the standing position. Most of these patients have varying degrees of reduced blood volume. We tested the hypothesis that the relationship previously found between plasma volume and diastolic blood pressure in pressor states would also hold in orthostatic intolerance. We studied 16 patients with a history of symptomatic orthostatic intolerance associated with an elevation in plasma norepinephrine in the upright posture and hypovolemia in 9 patients and normovolemia in 7 patients. Our studies demonstrate an inverse relationship between plasma volume and diastolic blood pressure in patients with orthostatic intolerance. This finding also holds for the change in diastolic blood pressure in response to upright posture. In this relationship, patients with orthostatic intolerance with high plasma norepinephrine resemble those with essential hypertension, renovascular hypertension, and pheochromocytoma. We conclude that in a variety of conditions at both ends of the blood pressure spectrum, the seemingly paradoxical association of hypovolemia and diastolic blood pressure is preserved.

Relation of Blood Volume and Blood Pressure in Orthostatic Intolerance

A complex but crucial relationship exists between blood volume and blood pressure in human subjects; it has been recognized that in essential hypertension, renovascular hypertension, and pheochromocytoma, the relationship between plasma volume and diastolic blood pressure is an inverse one. This phenomenon has not been studied in individuals with low normal and reduced blood pressures. Orthostatic intolerance is a commonly encountered abnormality in blood pressure regulation often associated with tachycardia in the standing position. Most of these patients have varying degrees of reduced blood volume. We tested the hypothesis that the relationship previously found between plasma volume and diastolic blood pressure in pressor states would also hold in orthostatic intolerance. We studied 16 patients with a history of symptomatic orthostatic intolerance associated with an elevation in plasma norepinephrine in the upright posture and hypovolemia in 9 patients and normovolemia in 7 patients. Our studies demonstrate an inverse relationship between plasma volume and diastolic blood pressure in patients with orthostatic intolerance. This finding also holds for the change in diastolic blood pressure in response to upright posture. In this relationship, patients with orthostatic intolerance with high plasma norepinephrine resemble those with essential hypertension, renovascular hypertension, and pheochromocytoma. We conclude that in a variety of conditions at both ends of the blood pressure spectrum, the seemingly paradoxical association of hypovolemia and diastolic blood pressure is preserved.

Psychophysiological stress reactions in female and male urban bus drivers.

Male and female urban bus drivers were studied at work during everyday bus driving in urban traffic (work condition) and watching educational programs (comparison condition). The results showed that (a) both sexes had significantly higher adrenaline, noradrenaline, and cortisol excretion levels during work than during the comparison session; (b) during work and inactivity, there were no significant sex differences in hormone excretion for either hormone; (c) the percentage increase during work compared with control levels for all hormones was equally high in the female group as in the male group; and (d) there were no significant sex differences in self-reported mood (distress, well-being, control) during bus driving. The results are discussed in terms of type and intensity of stressors, gender differences in costs of adaptation, preventive measures, and the role of social influences in psychoneuroendocrine regulation.

Olfaction and human neonatal behaviour: clinical implications

About 1–2% of the human genome is allocated to production of receptors for the olfactory epithelium–a hint as to the possible importance of this chemical sense, which includes two anatomically distinct systems: the main olfactory system with sensory cells located in the upper part of the nasal cavity, and the vomeronasal organ with sensory cells on the nasal septum. In adults, individual odours may influence mate preferences and a growing body of evidence indicates that naturally occurring odours play an important role in the mediation of the infant's behaviour. Even foetal olfactory learning seems to occur and breast odours from the mother exert a pheromone‐like effect at the newborn's first attempt to locate the nipple. Newborns are generally responsive to breast odours produced by lactating women. Olfactory recognition may be implicated in the early stages of the mother‐infant attachment process, when the newborns learn to recognize the own mother's unique odour signature–a process possibly facilitated by the high norepinephrine release and the arousal of the locus coeruleus at birth. New knowledge about human odour physiology may have diagnostic and therapeutic implications–the initiation and stabilization of breastfeeding and termination of apnoeic spells are mentioned as examples.

Olfaction and human neonatal behaviour: clinical implications.

About 1-2% of the human genome is allocated to production of receptors for the olfactory epithelium--a hint as to the possible importance of this chemical sense, which includes two anatomically distinct systems: the main olfactory system with sensory cells located in the upper part of the nasal cavity, and the vomero-nasal organ with sensory cells on the nasal septum. In adults, individual odours may influence mate preferences and a growing body of evidence indicates that naturally occurring odours play an important role in the mediation of the infant's behaviour. Even foetal olfactory learning seems to occur and breast odours from the mother exert a pheromone-like effect at the newborn's first attempt to locate the nipple. Newborns are generally responsive to breast odours produced by lactating women. Olfactory recognition may be implicated in the early stages of the mother-infant attachment process, when the newborns learn to recognize the own mother's unique odour signature--a process possibly facilitated by the high norepinephrine release and the arousal of the locus coeruleus at birth. New knowledge about human odour physiology may have diagnostic and therapeutic implications--the initiation and stabilization of breastfeeding and termination of apnoeic spells are mentioned as examples.

Responses of catecholestrogen metabolism to acute graded exercise in normal menstruating women before and after training.

It has been hypothesized that exercise-related hypo-estrogenemia occurs as a consequence of increased competition of catecholestrogens (CE) for catechol-O-methyltransferase (COMT). This may result in higher norepinephrine (NE) concentrations, which could interfere with normal gonadotropin pulsatility. The present study investigates the effects of training on CE responses to acute exercise stress. Nine untrained eumenorrheic women (mean percentage of body fat +/-SD: 24.8 +/- 3.1%) volunteered for an intensive 5-day training program. Resting, submaximal, and maximal (tmax) exercise plasma CE, estrogen, and catecholamine responses were determined pre- and post training in both the follicular (FPh) and luteal phase (LPh). Acute exercise stress increased total primary estrogens (E) but had little effect on total 2-hydroxyestrogens (2-OHE) and 2-hydroxyestrogen-monomethylethers (2-MeOE) (= O-methylated CE after competition for catechol-O-methyltransferase). This pattern was not significantly changed by training. However, posttraining LPh mean (+/-SE) plasma E, 2-OHE, and 2-MeOE concentrations were significantly lower (P < 0.05) at each exercise intensity (for 2-OHE: 332 +/- 47 vs. 422 +/- 57 pg/mL at tmax; for 2-MeOE: 317 +/- 26 vs. 354 +/- 34 pg/mL at tmax). Training produced opposite effects on 2-OHE:E ratios (an estimation of CE formation) during acute exercise in the FPh (reduction) and LPh (increase). The 2-MeOE:2-OHE ratio (an estimation of CE activity) showed significantly higher values at tmax in both menstrual phases after training (FPh: +11%; LPh: +23%; P < 0.05). After training, NE values were significantly higher (P < 0.05). The major findings of this study were that: training lowers absolute concentrations of plasma estrogens and CE; the acute exercise challenge altered plasma estrogens but had little effect on CE; estimation of the formation and activity of CE suggests that formation and O-methylation of CE proportionately increases. These findings may be of importance for NE-mediated effects on gonadotropin release.

Structural properties of rat mesenteric small arteries after 4-wk exposure to elevated or reduced blood flow

We determined the structure of mesenteric small arteries after chronic elevation and chronic reduction of blood flow. In 6-wk-old rats, we ligated second-order side branches of every other first-order side branch of the superior mesenteric artery. This persistently reduced blood flow (-90%) in the vessels feeding into the ligated trees and elevated blood flow (+80%) in the nonligated mesenteric artery side branches. Four weeks after surgery, vessels that had been exposed to high blood flow (HF) or low blood flow (LF) and vessels from sham-operated rats (Sham) were isolated and mounted in a pressure myograph system. At an intraluminal pressure of 100 mmHg, the internal diameter at rest was larger in HF (533 +/- 23 microm) and smaller in LF (262 +/- 14 microm) than in Sham vessels (427 +/- 15 microm). Also, wall and media cross-sectional areas were larger in HF and smaller in LF than in Sham vessels (media: 22 +/- 1, 11 +/- 2, and 16 +/- 1 x 10(3) microm2, respectively), but circumferential wall stress did not differ among groups. DNA content was significantly increased in HF vessels (+100%) and was not modified in LF vessels. Maximal vasoconstrictions elicited by high potassium or norepinephrine were slightly increased in HF vessels but were reduced by 50% in LF vessels. Thus chronic changes in blood flow give rise to structural changes that normalize circumferential wall stress. Elevated blood flow resulted in outward hypertrophic remodeling involving hyperplasia. Reduced blood flow resulted in inward hypotrophic remodeling accompanied by hyporeactivity of the arterial smooth muscle.

Coronary arterial hyperreactivity and mesenteric arterial hyporeactivity after myocardial infarction in the rat.

After myocardial infarction, several neurohumoral systems become activated to maintain systemic perfusion pressure. We evaluated whether this leads to alterations of wall structure and contractile reactivity in the thoracic aorta, coronary septal artery, and mesenteric resistance arteries. In male Wistar rats, myocardial infarction (MI) was induced by permanent ligation of the left coronary artery. At 5 weeks after MI or sham operation, vessel segments were isolated, chemically sympathectomized, and mounted in a myograph for recording of isometric force development. Contractile reactivity to high potassium, norepinephrine, phenylephrine, serotonin, and Arg-vasopressin was determined. At the end of the experiments, vessels were fixed for morphometric analysis (cross-sectional area, media thickness, radius, and wall-to-lumen ratio). At 5 weeks after myocardial infarction, no alterations of contractile reactivity or wall structure were observed in the thoracic aorta of MI rats. In mesenteric resistance arteries, a nonselective reduction of maximal active wall tension and of active wall stress in response to vasoconstrictors was observed, whereas vessel wall structure and sensitivity to stimuli were not modified. On the other hand, coronary septal arteries displayed hyperreactivity to all strong contractile stimuli. These observations demonstrate a heterogeneity of arterial reactivity changes at 5 weeks after MI in the rat: (a) no alterations in thoracic aorta, (b) hyporeactivity of mesenteric resistance arteries despite maintenance of media mass, and (c) hyperreactivity of coronary vessels obtained from the hypertrophic remnant myocardium. This could result from the complex regional hemodynamic and neurohumoral changes associated with heart failure and may contribute to the further deterioration of cardiovascular function in this setting.

Plasma catecholamines in pre- and in postmenopausal women with mild to moderate essential hypertension

The sympathetic nervous system (SNS) is thought to play an important role in the pathogenesis of essential hypertension and many studies have established a relationship between plasma levels of norepinephrine (NE) and epinephrine (E) and sympathetic nervous activity (SNA). Furthermore, it has been suggested that climacteric women are more exposed to psychosocial stress which can produce a transient rise in blood pressure (BP) and, with time, determine a hypertensive state. Plasma NE and E levels were measured at rest and after physiological stimulation (head-up tilt test) in 20 hypertensive (BP: 146 +/- 13/101 +/- 4 mm Hg) and in 20 normotensive women (BP: 132 +/- 7/85 +/- 4 mm Hg). Women in each of these two groups were further subdivided according to their climacteric status (10 premenopausal and 10 postmenopausal women). No difference in NE values at rest was found between groups and subgroups. During head-up tilt test, Ln NE plasma values increased in normotensive and hypertensive groups; the rise was significantly higher in hypertensive than in normotensive women (P < 0.01). In climacteric subgroups, Ln NE appeared markedly increased above resting levels in pre- and postmenopausal hypertensive women when their position was changed from supine to upright (P < 0.01). Since high plasma NE levels after stimulation (head-up tilt) are associated with sympathetic overactivity, we conclude that SNA is involved in the pathogenesis of essential hypertension in climacteric women.