Circulating Catecholamine Concentrations Research Articles

The polyphenol epigallocatechin gallate lowers circulating catecholamine concentrations and alters lipid metabolism during graded exercise in man: a randomized cross-over study

PurposePhysical exercise is shown to mitigate catecholamine metabolites; however, it is unknown if exercise-induced increases in sympatho-adrenal activity or catecholamine metabolites are influenced by ingestion of specific catechins found within green tea. This study explored the impact of epigallocatechin gallate (EGCG) ingestion on catecholamine metabolism during graded cycle exercise in humans.MethodsEight males (22.4 ± 3.3 years, BMI:25.7 ± 2.4 kg.m2) performed a randomised, placebo-controlled, single-blind, cross-over trial after consumption (1450 mg) of either EGCG or placebo (PLAC) and performed graded cycling to volitional exhaustion. Venous bloods were taken at rest, 2 h post-ingestion and after every 3-min stage. Blood variables were analysed for catecholamines, catecholamine metanephrines and metabolic variables at rest, 2 h post-ingestion (POST-ING), peak rate of lipid oxidation (FATpeak), lactate threshold (LT) and peak rate of oxygen consumption (VO2peak). Data were analysed using SPSS (Version 26).ResultsResting catecholamine and metanephrines were similar between trials. Plasma adrenaline (AD) was lower in ECGC treatment group between trials at FATpeak (P < 0.05), LT (P < 0.001) and VO2peak (P < 0.01). Noradrenaline (NA) was lower under EGCG at POST (P < 0.05), FATpeak (P < 0.05), LT (P < 0.01) and VO2peak (P < 0.05) compared to PLAC. Metanephrines, glucose and lactate increased similarly with exercise intensity in both trials. Lipid oxidation rate was 32% lower in EGCG at FATpeak (EGCG 0.33 ± 0.14 vs. PLAC 0.49 ± 0.11 g.min−1, P < 0.05). Cycle time to exhaustion was similar (NS).ConclusionAcute EGCG supplementation reduced circulating catecholamines but not; metanephrine, glucose or lactates, response to graded exercise. Lower circulating catecholamines may explain a lower lipid oxidation rate.

Neuroendocrine responses to early life stress and trauma and susceptibility to disease

ABSTRACTThe term ‘early life stress’ has been used to describe a broad spectrum of adverse exposures during foetal life, childhood and adolescence. Early life stress and trauma are associated with a higher risk for later mental and physical health disorders, such as anxiety, depression, and post-traumatic stress disorder (P.T.S.D.) as well as cardiometabolic and inflammatory diseases and chronic pain syndromes. The objective of this brief review is to investigate the neuroendocrine responses to early life stress and their role as biological predisposing factors for later disease.Stress-related neuroendocrine alterations in response to early adversity include hyper- or hypo-activation of the stress system and may persist or worsen in later life, acting as biological vulnerability factors for the development of later disease. A key effect of stress during foetal life, childhood, and adolescence is that it programmes the developing brain, especially brain structures involved in stress reactions, such as the prefrontal cortex, the hippocampus, and the amygdala, to hyper- or hypo-react to ensuing stressors. Animal studies have shown that chronically elevated stress mediators may lead to alterations in brain development through mechanisms of accelerated loss of neurons, delays in myelination, or abnormalities in developmentally appropriate neural synaptic pruning. Critical periods of brain development represent time-windows of elevated synaptic plasticity, mediating vulnerability, or establishing resilience to stress.Stress is generally associated with acute activation of the hypothalamic-pituitary-adrenal (H.P.A.) axis and the arousal/sympathetic nervous system, as evidenced, in most studies, by elevated cortisol and catecholamine concentrations in the periphery. However, the chronic and/or intense experience of stress may be associated with chronic hyper- or hypo-activation of mediators of the stress system. This chronic condition represents dyshomeostasis, also called allostasis or cacostasis, which is related to further morbidity, such as obesity and the metabolic syndrome, diabetes mellitus type 2, atherosclerosis, osteoporosis, and immune dysfunction (Pervanidou & Chrousos, 2012).P.T.S.D., the most common stress-related disorder, is typically associated with increased secretion of corticotropin-releasing hormone centrally, with paradoxically decreased cortisol secretion peripherally, and elevated circulating catecholamine concentrations. Stress-related neuroendocrine alterations during early life might result in conditions characterized by chronic hypo-activation of the H.P.A. axis, as typically observed in P.T.S.D. and atypical depression. Scarce data exist on the longitudinal course of P.T.S.D. development and maintenance, beginning from the exposure to the traumatic event. We investigated the natural history of neuroendocrine changes in relation to P.T.S.D. development in children and adolescents experiencing a motor vehicle accident. This longitudinal study provided evidence for an initial elevation of evening salivary cortisol and an alteration in cortisol circadian secretion in response to the experience of an intense stressor. This initial alteration was followed by a gradual normalization of cortisol with time, leading potentially to decreased cortisol concentrations in the periphery, months or years after the traumatic exposure. At the same time, a progressive elevation of circulating norepinephrine (N.E.) was noted in children that continued to exhibit P.T.S.D. This longitudinal interaction of peripheral cortisol and NE concentrations seems to characterize those that develop and maintain P.T.S.D. (Pervanidou et al., 2007). Thus, low cortisol, together with high N.E. concentrations, that characterize adult P.T.S.D., may be the end stage of the disorder. These data are also in accordance with findings in adults, showing hypocortisolism in the aftermath of a stressful experience to predict P.T.S.D. development.Several parameters affect the direction of the H.P.A. axis (increased or decreased cortisol production) in P.T.S.D., and among them, previous trauma and time since the trauma occurred seem to be crucial determinants of hyper- or hypo- activation of the H.P.A. axis. Other parameters include: genetic and epigenetic vulnerability; transgenerational actions; environmental influences in the management of early life stress; the nature, severity, and duration of the traumatic event; the developmental stage, age at the time of trauma; and comorbidities (Pervanidou, 2008).In conclusion, early life stress exposures result in neuroendocrine alterations and programming of the neuronal networks of the brain, acting as predisposing factors for further mental and physical health problems.

Hydrogen sulfide stimulates catecholamine secretion in rainbow trout (Oncorhynchus mykiss)

We tested the hypothesis that endogenously produced hydrogen sulfide (H(2)S) can potentially contribute to the adrenergic stress response in rainbow trout by initiating catecholamine secretion from chromaffin cells. During acute hypoxia (water Po(2) = 35 mmHg), plasma H(2)S levels were significantly elevated concurrently with a rise in circulating catecholamine concentrations. Tissues enriched with chromaffin cells (posterior cardinal vein and anterior kidney) produced H(2)S in vitro when incubated with l-cysteine. In both tissues, the production of H(2)S was eliminated by adding the cystathionine beta-synthase inhibitor, aminooxyacetate. Cystathionine beta-synthase and cystathionine gamma-lyase were cloned and sequenced and the results of real-time PCR demonstrated that with the exception of white muscle, mRNA for both enzymes was broadly distributed within the tissues that were examined. Electrical field stimulation of an in situ saline-perfused posterior cardinal vein preparation caused the appearance of H(2)S and catecholamines in the outflowing perfusate. Perfusion with the cholinergic receptor agonist carbachol (1 x 10(-6) M) or depolarizing levels of KCl (1 x 10(-2) M) caused secretion of catecholamines without altering H(2)S output, suggesting that neuronal excitation is required for H(2)S release. Addition of H(2)S (at concentrations exceeding 5 x 10(-7) M) to the perfusion fluid resulted in a marked stimulation of catecholamine secretion that was not observed when Ca(2+)-free perfusate was used. These data, together with the finding that H(2)S-induced catecholamine secretion was unaltered by the nicotinic receptor blocker hexamethonium, suggest that H(2)S is able to directly elicit catecholamine secretion via membrane depolarization followed by Ca(2+)-mediated exocytosis.

Effects of Pioglitazone Versus Glipizide on Body Fat Distribution, Body Water Content, and Hemodynamics in Type 2 Diabetes

Pioglitazone, a peroxisome proliferator-activated receptor agonist and glipizide, an insulin secretagogue, are commonly used to treat type 2 diabetes. Our study was designed to examine the effects of pioglitazone versus glipizide on body water, body composition, and hemodynamic parameters in the presence of comparable glycemic control between groups. We studied 19 diabetic subjects randomly assigned to either 45 mg pioglitazone (n = 8) or 10 mg (median dose) glipizide (n = 11) for 12 weeks. Body water content was measured with deuterated water, body composition by dual-energy X-ray absorptiometry and computed tomography, and cardiac output and systemic vascular resistance by acetylene rebreathing technique both before and after therapy. Pioglitazone increased (P < 0.001 from baseline) total body water (+2.4 +/- 0.5 l) accounting for 75% of the total weight gain (+3.1 +/- 2.0 kg) but did not alter vascular endothelial growth factor concentrations. Total abdominal (-32.2 +/- 19 cm(2)) and visceral fat area (-16.1 +/- 8 cm(2)) tended to decrease with pioglitazone but increased (P < 0.02 for differences between groups) with glipizide (+38.4 +/- 17 cm(2) abdominal; +19.1 +/- 9 cm(2) visceral). Pioglitazone tended to reduce (P = 0.05) diastolic (-8.4 +/- 4 mmHg) and mean (-9.5 +/- 5 mmHg; P = 0.08) blood pressure and reduced (P < 0.001) systemic vascular resistance (2,785 +/- 336 vs. 2,227 +/- 136 dynes/s per m(2)), while there were no differences in these parameters with glipizide. Neither therapy altered circulating catecholamine concentrations. When pioglitazone and glipizide are given in doses sufficient to achieve equivalent glycemic control in people with type 2 diabetes, pioglitazone increases total body water, thereby accounting for the majority of weight gain, tended to decrease visceral and abdominal fat content and blood pressure, and reduces systemic vascular resistance.

Radionuclide Imaging Metabolic Activity of Brown Adipose Tissue in a Patient with Pheochromocytoma

We describe a patient with extra-adrenal pheochromocytoma and high plasma norepinephrine levels. Radionuclide images of this patient obtained using (18)F-fluorodeoxyglucose and (123)I-metaiodobenzylguanidine revealed bilateral tracer accumulation in the shoulder and lower neck. The regions of radiotracer uptake corresponded to the location of human brown adipose tissue (BAT). Excessive sympathetic stimulation by high circulating catecholamine concentrations augmented the metabolic activity and tracer uptake in the BAT. This study showed that radionuclide imaging can noninvasively visualize human BAT in terms of metabolic and functional activity.

The effects of ractopamine on the behavior and physiology of finishing pigs.

The objectives of this study were to examine the effects of ractopamine (RAC) on the behavior and physiology of pigs during handling and transport. Twenty-four groups of three gilts were randomly assigned to one of two treatments 4 wk before slaughter: finishing feed plus RAC (10 ppm) or finishing feed alone. Pigs were housed in the same building in adjacent pens with fully slatted floors and ad libitum access to feed and water. Behavioral time budgets were determined in six pens per treatment over a single 24-h period during each week. Behavioral responses of these pigs to routine handling and weighing were determined at the start of the trial and at the end of each week. Heart-rate responses to unfamiliar human presence were measured in all pigs and blood samples were taken from a single pig in each pen on different days during wk 4. At the end of wk 4, all pigs were transported for 22 min to processing. Heart rate was recorded from at least one pig per pen during transport and a postmortem blood sample was taken from those pigs that were previously sampled. During wk 1 and 2, RAC pigs spent more time active (P < 0.05), more time alert (P < 0.05), and less time lying in lateral recumbency (P < 0.05). They also spent more time at the feeder in wk 1 (P < 0.05). At the start of the trial, there were no differences in behavioral responses to handling. However, over each of the next 4 wk, fewer RAC pigs exited the home pen voluntarily, they took longer to remove from the home pen, longer to handle into the weighing scale and needed more pats, slaps, and pushes from the handler to enter the scales. At the end of wk 4, RAC pigs had higher heart rates in the presence of an unfamiliar human (P < 0.05) and during transport (P < 0.05), but not during loading and unloading. Also at the end of wk 4, RAC pigs had higher circulating catecholamine concentrations (P < 0.05) than control pigs. Circulating cortisol concentrations and cortisol responses to transport did not differ between treatments. The results show that ractopamine affected behavior, heart rate, and catecholamine profile of finishing pigs and made them more difficult to handle and potentially more susceptible to handling and transport stress.

Catecholamine response during haemodynamically stable upright posture in individuals with and without tilt-table induced vasovagal syncope.

Changes in circulating catecholamine concentrations during vasovagal faints have been the subject of considerable study. However, whether catecholamines are part of the triggering mechanism, or principally reflect attempted compensation for an evolving circulatory crisis is unknown. To address this issue, we determined whether the circulating catecholamine response to upright posture differs among patients with and without inducible vasovagal faints at a time when there is no detectable haemodynamic compromise. Blood samples for measurement of adrenaline and noradrenaline (Norepi) concentrations were obtained in the baseline state, and at both 2-3 min and 4-6 min of upright posture in 22 patients undergoing head-up tilt-table testing for evaluation of syncope of unknown cause. In 11 individuals tilt-testing induced syncope at >5 min head-up posture (Group 1). In 11 other individuals tilt testing did not result in syncope (Group 2). Supine arterial catecholamine levels were comparable in the two groups. However, adrenaline concentrations during upright posture tended to be greater at 2-3 min and were significantly greater at 4-6 min in Group 1 than in Group 2 (P< 0.01). These differences occurred in the absence of significant intergroup differences in mean arterial pressure or cardiac cycle lengths. Norepi concentrations also increased in both groups, but without significant differences. Circulating adrenaline concentrations in posturally induced vasovagal faints rise more rapidly in vasovagal fainters than in comparably posturally stressed non-fainters, and were significantly greater in fainters prior to either detectable haemodynamic compromise or diminution of circulating Norepi levels. These findings suggest that a premonitory rise in adrenaline concentrations occurs in vasovagal fainters unassociated with an evolving circulatory crisis.

Sickle cell disease in pregnancy

Sickle cell disease in pregnancy

Clinical Factors Influencing Blood Pressure in the Neonate

After completing this article, readers should be able to: 1. Describe the association between gestational age, birthweight, and postnatal age and blood pressure in the neonate. 2. Delineate the primary clinical consideration in an infant who has hypotension. 3. Describe the controversy surrounding the relationship between antenatal steroid therapy and neonatal blood pressure. 4. Delineate the aspects of management of respiratory illnesses in the neonate that may be associated with altered blood pressure. 5. List factors that may cause altered blood pressure in the neonate. Few aspects of neonatal care have generated as much controversy as the assessment of blood pressure (BP) and need for treatment of perceived abnormalities of this physiologic variable. Familiarity with clinical situations in which BP may be low should allow anticipation of this common clinical problem and timely intervention when such treatment is necessary (Tables 1 and 2). In this article, we review factors that have been shown to have the greatest effect on BP. View this table: Table 1. Some Risk Factors for Shock in the Newborn View this table: Table 2. Some Causes of Cardiogenic Shock in the Newborn A direct reading from an indwelling arterial catheter represents the “gold standard” for measuring BP in the neonate, and this method should be used whenever possible. Obviously, arterial access may not always be available, and the ability to monitor BP noninvasively using an oscillometric technique represents a major advancement in neonatal care. The correlation between direct and indirect methods generally has been good. Disparities in results have been related to various factors, including inappropriate cuff width-to-arm ratio or problems with the arterial catheter-transducer system, such as air bubbles or clots. In general, indirect determinations are higher than those obtained directly, often by 3 to 5 mm Hg. The individual contributions of birthweight and gestational age to BP are difficult to delineate. Several groups of investigators have shown that BP …

Effect of the α2-Agonist Dexmedetomidine on Cerebral Neurotransmitter Concentrations during Cerebral Ischemia in Rats

This study investigates whether neuroprotection seen with dexmedetomidine is associated with suppression of peripheral or central sympathetic tone. Thirty fasted male Sprague-Dawley rats were intubated and ventilated with isoflurane and N2O/O2 (fraction of inspired oxygen = 0.33). Catheters were inserted into the right femoral artery and vein and into the right jugular vein. Cerebral blood flow was measured using laser Doppler flowmetry. Bilateral microdialysis probes were placed into the cortex and the dorsal hippocampus. At the end of preparation, the administration of isoflurane was replaced by fentanyl (bolus: 10 microg/kg; infusion: 25 microg x kg(-1) x h(-1)). Animals were randomly assigned to one of the following groups: group 1 (n = 10): control animals; group 2 (n = 10): 100 microg/kg dexmedetomidine administered intraperitoneally 30 min before ischemia; group 3 (n = 10): sham-operated rats. Ischemia (30 min) was produced by unilateral carotid artery occlusion plus hemorrhagic hypotension to a mean arterial blood pressure of 30-35 mmHg to reduce ipsilateral cerebral blood flow by 70%. Pericranial temperature, arterial blood gases, and pH were maintained constant. Cerebral catecholamine and glutamate concentrations and plasma catecholamine concentrations were analyzed using high-performance liquid chromatography. During ischemia, dexmedetomidine suppressed circulating norepinephrine concentrations by 95% compared with control animals. In contrast, brain norepinephrine and glutamate concentrations were increased irrespective of dexmedetomidine infusion before ischemia. The current data show that the increase of circulating catecholamine concentrations during cerebral ischemia was suppressed with dexmedetomidine. In contrast, dexmedetomidine does not suppress elevation in brain norepinephrine and glutamate concentration associated with cerebral ischemia. This suggests that the neuroprotective effects of dexmedetomidine are not related to inhibition of presynaptic norepinephrine or glutamate release in the brain.

Norepinephrine-induced aortic hyperplasia and extracellular matrix deposition are endothelin-dependent.

Sympathetic hyperactivity is observed in several disease states and may contribute to cardiovascular hypertrophic remodeling. Endothelin has been suggested to be a mediator of hypertrophy. To examine the involvement of endothelin in maintaining the growth response induced by exogenous norepinephrine. Rats were treated with norepinephrine (2.5 microg/Kg per min subcutaneously) for 2 and 4 weeks, alone or in association with the selective endothelin-A (ETA) receptor antagonist, darusentan (LU135252, 30 mg/Kg per day orally) for weeks 3 and 4. Increases in medial cell number and accumulation of collagen and elastin characterized norepinephrine-induced aortic remodeling. These effects occurred without marked changes of mean arterial pressure, but may be related to enhanced pressure variability in addition to direct effects of norepinephrine. Inhibition of ETA receptors by darusentan reversed aortic alterations produced by infusion of norepinephrine. Evaluation of medial apoptosis did not reveal any significant change in any group at 4 weeks. Antagonism of ETA receptors effectively and rapidly reversed norepinephrine-induced aortic structural and compositional changes, suggesting a central role of endothelin in mediating this response. Thus, ETA receptor antagonists may help to regress large artery remodeling in conditions of increased circulating catecholamine concentrations.

Stress-Induced Catecholamine Changes in the Hemolymph of the Oyster Crassostrea gigas

The stress response is a series of coordinated physiological reactions increasing an organism's capacity to maintain homeostasis in the presence of threatening agents. This fundamental process is known to involve hormonal signaling to rapidly modulate key physiological functions in vertebrates, but data are lacking concerning neuroendocrine responses to stress in invertebrates. The present study examined circulating catecholamine (CA) responses to stress in oysters. Mechanical disturbances (consisting of shaking the animals) and temperature or salinity variations were applied to the animals because these three types of stressors are commonly encountered by oysters in aquaculture or in their natural habitat. Results show that both circulating noradrenaline (NA) and dopamine (DA) concentrations increased in response to stress. The catecholaminergic response to acute mechanical stressors was rapid (less than 5 min), transient (a return to basal CA levels was observed after 60-90 min), and reflected both the intensity and duration of the perturbation. In contrast, responses to temperature and salinity variations were long lasting (up to 72 h). CA concentrations varied from 1.61 +/- 0.30 ng NA/ml and 0.41 +/- 0.05 ng DA/ml to maximal values of 22.07 +/- 0.97 ng NA/ml and 2.24 +/- 0.19 ng DA/ml. Such CA concentrations are known to induce physiological responses in bivalves, suggesting that stress-induced NA and DA changes exert a regulatory function in oysters.

Catecholamine levels and receptor expression in low protein rat offspring.

Low birthweight in humans has been shown to lead to increased resting pulse rate in adult life, suggesting possible increased sympathoadrenal activity. The hypothesis that early growth restriction is associated with permanent alterations in catecholamine metabolism was tested. Circulating catecholamine concentrations (by radioimmunoassay) and adipocyte adrenoceptor expression from different fat depots (by Western blot) were estimated in 12-week-old male offspring of rat dams fed a reduced protein diet during pregnancy and lactation. In the fed state, median (interquartile range) plasma adrenaline concentrations for male control and low protein offspring rats were: 0.65 (0.48-0.86) vs. 1.42 (0.89-1.87) nmol/l (P < 0.005), respectively. Equivalent noradrenaline concentrations were: 2.71 (2.16-3.46) vs. 3.45 (3.00-4.28) nmol/l (P < 0.05). After 24 h starvation, plasma adrenaline concentrations of controls rose to become similar to those of low protein offspring: 1.03 (0.95-1.31) vs. 1.41 (0.69-1.62) nmol/l (P = 0.3), respectively. Noradrenaline concentrations rose in both groups to become similar: 3.84 (3.33-4.54) vs. 4.32 (3.70-6.54) nmol/l (P = 0.3). In epididymal adipocytes adrenoceptor expression (relative to that of controls) was: alpha2A 0.79 (0.66-0.94) (P = 0.08), beta1 2.60 (2.27-3.07) (P = 0.04), beta3 1.37 (1.27-1.46) (P = 0.02). Similar-pattern differences in adrenoceptor expression were observed in subcutaneous and intra-abdominal adipocytes. These results are consistent with the suggestion that long-term alterations in catecholamine metabolism are present in adult offspring of rats fed a reduced protein diet during pregnancy and lactation.

Desensitisation of chromaffin cell nicotinic receptors does not impede catecholamine secretion during acute hypoxia in rainbow trout (Oncorhynchus mykiss).

Experiments were performed on adult rainbow trout (Oncorhynchus mykiss) in vivo using chronically cannulated fish and in situ using a perfused posterior cardinal vein preparation (i) to characterise the desensitisation of chromaffin cell nicotinic receptors and (ii) to assess the ability of fish to secrete catecholamines during acute hypoxia with or without functional nicotinic receptors. Intra-arterial injection of nicotine (6.0x10(-)(7 )mol kg(-)(1)) caused a rapid increase in plasma adrenaline and noradrenaline levels; the magnitude of this response was unaffected by an injection of nicotine given 60 min earlier. Evidence for nicotinic receptor desensitisation, however, was provided during continuous intravenous infusion of nicotine (1.3x10(-)(5 )mol kg(-)(1 )h(-)(1)) in which plasma catecholamine levels increased initially but then returned to baseline levels. To ensure that the decline in circulating catecholamine concentrations during continuous nicotine infusion was not related to changes in storage levels or altered rates of degradation/clearance, in situ posterior cardinal vein preparations were derived from fish previously experiencing 60 min of saline or nicotine infusion. Confirmation of nicotinic receptor desensitisation was provided by demonstrating that the preparations derived from nicotine-infused fish were unresponsive to nicotine (10(-)(5 )mol l(-)(1)), yet remained responsive to angiotensin II (500 pmol kg(-)(1)). The in situ experiments demonstrated that desensitisation of the nicotinic receptor occurred within 5 min of receptor stimulation and that resensitisation was established 40 min later. The ability to elevate plasma catecholamine levels during acute hypoxia (40-45 mmHg; 5.3-6.0 kPa) was not impaired in fish experiencing nicotinic receptor desensitisation. Indeed, peak plasma adrenaline levels were significantly higher in the desensitised fish during hypoxia than in controls (263+/-86 versus 69+/-26 nmol l(-)(1); means +/- s.e.m., N=6-9). Thus, the results of the present study demonstrate that activation of preganglionic sympathetic cholinergic nerve fibres and the resultant stimulation of nicotinic receptors is not the sole mechanism for eliciting catecholamine secretion during hypoxia.

Dietary copper effects on lipid metabolism and circulating catecholamine concentrations in finishing steers.

Forty-eight Angus and Hereford x Angus steers were used to determine the effects of copper (Cu) on lipid and catecholamine metabolism. Steers were stratified by weight within breed and randomly assigned to treatments. Treatments consisted of 0 (control, no supplemental Cu), 10, or 40 mg of supplemental Cu (from Cu2(OH)3Cl)/kg DM. Steers were fed a corn silage-soybean meal-based growing diet for 42 d. Animals were then switched to a high-concentrate finishing diet and remained on the same dietary treatments. On d 70, indwelling jugular catheters were nonsurgically inserted into five steers per treatment. Blood samples were obtained from steers after a 24-h period of feed withdrawal, 1 h after feeding, and after i.v. administration of norepinephrine and were subsequently analyzed for nonesterified fatty acid (NEFA) and catecholamine concentrations. Average daily gain over the finishing period was higher (P < 0.06) in steers receiving supplemental Cu. Serum total cholesterol concentrations were reduced (P < 0.05) on d 84 and 112 in steers supplemented with Cu. Serum norepinephrine (P < 0.14) and NEFA concentrations following feed withdrawal tended (P < 0.12) to be higher in Cu-supplemented steers. Postfeeding norepinephrine concentrations tended to be higher (P < 0.14) in Cu-supplemented steers. Nonesterifled fatty acid concentrations were lower (P < 0.10) in Cu-supplemented steers after norepinephrine administration. Backfat depth was decreased (P < 0.10) and longissimus muscle polyunsaturated fatty acid percentages were increased (P < 0.10) in steers receiving supplemental Cu. These results indicate that Cu addition to a finishing diet containing 5 mg Cu/kg DM alters lipid metabolism. The reduction in backfat depth may be due to copper altering catecholamine metabolism in steers.

Insulin- and glucagon-independent effects of calcitonin gene—related peptide in the conscious dog

Calcitonin gene-related peptide (CGRP) causes vasodilation in many vascular beds, resulting in hypotension and tachycardia. The current studies were conducted in overnight-fasted conscious dogs to determine the effect of different CGRP dosages on carbohydrate metabolism and catecholamine release resulting from hemodynamic changes. During a pancreatic clamp, dogs received intraportal infusions of CGRP at 13, 26, and 52 (n = 3) or 52, 105, and 210 pmol x kg(-1) x min(-1) (n = 4; 60 minutes at each rate). Blood pressure decreased (P < .05) and the heart rate and hepatic blood flow (HBF) increased a maximum of 100% and 30%, respectively (P < .05). For the five CGRP infusion rates, arterial plasma epinephrine increased approximately 1.3-, 2.4-, 7.4-, 12-fold, and eightfold basal, respectively; norepinephrine increased about 2.3-, 3.3-, 4.1-, 4.6-, and 4.8-fold basal, respectively; and cortisol increased about twofold, 3.4-fold, fivefold, sixfold, and 6.2-fold basal, respectively. At CGRP infusion rates of 52 pmol x kg(-1) x min(-1) or higher, increases (P < .05) occurred for plasma glucose, endogenous glucose production (EndoRa), and net hepatic uptake of gluconeogenic substrates (maximum change, 24 mg/dL, 1.3 mg x kg(-1) x min(-1), and 9.9 micromol x kg(-1) x min(-1), respectively). Arterial blood glycerol concentrations increased only a maximum of 30%. At the two highest CGRP infusion rates, glycerol returned to basal concentrations and arterial plasma nonesterified fatty acids (NEFAs) decreased. The increased net hepatic uptake of gluconeogenic substrates during CGRP infusion was sufficient to account for 49% to 58% of the increase in EndoRa. CGRP has no apparent direct effects on hepatic carbohydrate metabolism, but the catecholamines, at levels similar to those observed during CGRP infusion, stimulate hepatic glycogenolysis. Therefore, some factor(s) other than CGRP, probably an increase in circulating catecholamine concentrations, would appear to be responsible for at least 42% to 51% of the increase in EndoRa.

Mediation of humoral catecholamine secretion by the renin-angiotensin system in hypotensive rainbow trout (Oncorhynchus mykiss).

The individual contributions of, and potential interactions between, the renin-angiotensin system (RAS) and the humoral adrenergic stress response to blood pressure regulation were examined in rainbow trout. Intravenous injection of the smooth muscle relaxant, papaverine (10 mg/kg), elicited a transient decrease in dorsal aortic blood pressure (PDA) and systemic vascular resistance (RS), and significant increases in plasma angiotensin II (Ang II) and catecholamine concentrations. Blockade of alpha-adrenoceptors before papaverine treatment prevented PDA and RS recovery, had no effect on the increase in plasma catecholamines, and resulted in greater plasma Ang II concentrations. Administration of the angiotensin-converting enzyme inhibitor, lisinopril (10(-4) mol/kg), before papaverine treatment attenuated the increases in the plasma concentrations of Ang II, adrenaline, and noradrenaline by 90, 79, and 40%, respectively and also prevented PDA and RS recovery. By itself, lisinopril treatment caused a gradual and sustained decrease in PDA and RS, and reductions in basal plasma Ang II and adrenaline concentrations. Bolus injection of a catecholamine cocktail (4 nmol/kg noradrenaline plus 40 nmol/kg adrenaline) in the lisinopril+papaverine-treated trout, to supplement their circulating catecholamine concentrations and mimic those observed in fish treated only with papaverine, resulted in a temporary recovery in PDA and RS. These results indicate that the RAS and the acute humoral adrenergic response are both recruited during an acute hypotensive stress, and have important roles in the compensatory response to hypotension in rainbow trout. However, whereas the contribution of the RAS to PDA recovery is largely indirect and relies on an Ang II-mediated secretion of catecholamines, the contribution from the adrenergic system is direct and relies at least in part on plasma catecholamines.

Sympathetic ganglionic blockade masks beneficial effect of isoflurane on histologic outcome from near-complete forebrain ischemia in the rat.

Isoflurane-anesthetized rats have better outcome from global cerebral ischemia than rats anesthetized with fentanyl and nitrous oxide. The authors wanted to determine whether circulating catecholamine concentrations depend on the anesthetic agent and whether sympathetic ganglionic blockade affects anesthetic-mediated differences in outcome from near-complete forebrain ischemia. For two different experiments, normothermic Sprague-Dawley rats that had fasted were assigned to one of four groups and subjected to 10 min of 30 mm Hg mean arterial pressure and bilateral carotid occlusion. Rats were anesthetized with 1.4% isoflurane or fentanyl (25 microg x kg(-1) x h(-1)) and 70% nitrous oxide, with or without preischemic trimethaphan (2.5 mg given intravenously). In experiment 1, arterial plasma catecholamine concentrations were measured before, at 2 and 8 min during, and after ischemia (n = 5-8). In experiment 2, animals (n = 15) underwent histologic analysis 5 days after ischemia. In experiment 1, intraischemic increases in plasma norepinephrine and epinephrine levels were 28 and 12 times greater in the fentanyl-nitrous oxide group than in the isoflurane group (P<0.01). Trimethaphan blocked all changes in plasma catecholamine concentrations (P<0.02). In experiment 2, isoflurane reduced the mean +/- SD percentage of dead hippocampal CA1 neurons compared with fentanyl-nitrous oxide (43+/-22% vs. 87+/-10%; P<0.001). Trimethaphan abolished the beneficial effects of isoflurane (91+/-6%; P<0.001). Similar observations were made in the cortex. Isoflurane attenuated the peripheral sympathetic response to ischemia and improved histologic outcome compared with fentanyl and nitrous oxide. This outcome benefit was reversed by sympathetic ganglionic blockade. The beneficial effects of isoflurane may result from a neuroprotective influence of an intermediate sympathetic response that is abolished by trimethaphan.

Impact of placental restriction on the development of the sympathoadrenal system.

We have investigated the impact of chronic restriction of placental function on circulating catecholamine concentrations and responses to the indirectly acting, sympathomimetic amine, tyramine, in the fetal sheep in late gestation. In 10 ewes, endometrial caruncles or placental placentation sites were removed before conception (placental restriction (PR) group). Fetal sheep in the PR group were hypoxemic throughout late gestation and growth-restricted (3.02 +/- 0.35 kg) when compared with control fetal sheep (4.30 +/- 0.29 kg; n = 8) at 140 d of gestation. Fetal plasma concentrations of noradrenaline and adrenaline were higher (p < 0.05) in the PR (7.06 +/- 3.17 pmol/mL and 2.89 +/- 2.01 pmol/mL, respectively) than in the control group (3.55 +/- 0.54 pmol/mL and 1.30 +/- 0.48 pmol/mL, respectively) throughout late gestation. Plasma noradrenaline, but not adrenaline concentrations, increased significantly between 110 and 140 d of gestation in both the PR and control group, and there was a significant inverse relationship between plasma noradrenaline and arterial PO2 in the PR and control groups (plasma noradrenaline = 12.34 - 0.40 PO2). In the PR group, plasma noradrenaline increased (p < 0.05) after tyramine infusion from 4.51 +/- 1.28 pmol/mL to a peak of 19.40 +/- 3.56 pmol/mL. In the control group, noradrenaline increased from 2.08 +/- 0.30 pmol/mL to a peak of 12.23 +/- 1.67 pmol/mL after tyramine infusion. There was no difference, however, in the maximal proportional changes in plasma noradrenaline concentrations in the PR (319 +/- 55%) and control (449 +/- 100%) groups after tyramine. We conclude that the most likely source of the increased plasma catecholamines in the PR group is enhanced catecholamine synthesis and secretion from developing sympathetic neurons.

Physiological inactivation of vasoactive hormones in rainbow trout

Hormone titers are affected by interplay between secretion and inactivation processes. While secretion is a focal process, inactivation mechanisms are often complex and poorly understood. In the present study, inactivation of cardiovascular regulatory hormones was examined from a physiological perspective by analyzing the half-time (t½) for recovery of dorsal and ventral aortic and central venous pressure, cardiac output, heart rate, and systemic and branchial vascular resistance following infusion or injection of hormones into conscious rainbow trout, Oncorhynchus mykiss. When possible, these were compared to recovery t½ of isolated vessel rings in vitro. The t½ for epinephrine or norepinephrine recovery in vivo was 3–4 min, approximately twice as long as recovery t½ for isolated celiacomesenteric and epibranchial artery rings in vitro. Thus, the rate-limiting step in vascular relaxation is the concentration of circulating catecholamine concentrations, and not metabolic or mechanical events within the vascular wall. The in vivo recovery t½ following angiotensin II (ANG II) infusion was 6–7 min, nearly twice that of catecholamines, but also greater than the t½ following bolus ANG II injection, inhibition of angiotensin converting enzyme with captopril or injection of trout bradykinin. Arginine vasotocin (AVT) recovery t½ in vivo, was considerably longer (20–30 min) than either catecholamine or ANG II t½ and longer than AVT recovery t½ of isolated vessels in vitro (5–6 min). The inactivation kinetics of catecholamines are consistent with circulatory convection-limited processes and do not appear to be limited by either tissue uptake or enzymatic degradation. This is probably the fastest type of ‘on-off’ endocrine regulation in fish. Inactivation of ANG II and bradykinin are also convection limited, but ANG II metabolism may become saturated with high doses of exogenous ANG II. AVT inactivation is not convection limited and may compensate for a quantitatively lower capacity of the pituitary for peptide secretion, or less emphasis on AVT as an on/off effector of vascular resistance. J. Exp. Zool. 279:254–264, 1997. © 1997 Wiley-Liss, Inc.