Biomedical subjects

David Robertson

Publications and source records attributed to David Robertson.

At least 19 recordsLinked to original sources

PubMed2007

An intimate interplay between precocious, migrating pericytes and endothelial cells governs human fetal brain angiogenesis.

In order to better understand the process of angiogenesis in the developing human brain, we have examined the spatial relationship and relative contributions of endothelial cells and pericytes, the two primary cell types involved in vessel growth, together with their relation with the vascular basement membrane. Pericytes were immunolocalized through use of the specific markers nerve/glial antigen 2 (NG2) proteoglycan, endosialin (CD248) and the platelet-derived growth factor receptor beta (PDGFR-beta), while endothelial cells were identified by the pan-endothelial marker CD31 and the blood brain barrier (BBB)-specific markers claudin-5 and glucose transporter isoform 1 (GLUT-1). The quantitative analysis demonstrates that microvessels of the fetal human telencephalon are characterized by a continuous layer of activated/angiogenic NG2 pericytes, which tightly invest endothelial cells and participate in the earliest stages of vessel growth. Immunolabelling with anti-active matrix metalloproteinase-2 (aMMP-2) and anti-collagen type IV antibodies revealed that aMMP-2 producing endothelial cells and pericytes are both associated with the vascular basement membrane during vessel sprouting. Detailed localization of the two vascular cell types during angiogenesis suggests that growing microvessels of the human telencephalon are formed by a pericyte-driven angiogenic process in which the endothelial cells are preceded and guided by migrating pericytes during organization of the growing vessel wall.

Basement Membrane↗

PubMed2007

Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: a morphologic, ultrastructural, immunohistochemical, and in situ hybridization analysis.

PURPOSE: The distribution and significance of caveolin 1 (CAV1) expression in different breast cell types and role in breast carcinogenesis remain poorly understood. Both tumor-suppressive and oncogenic roles have been proposed for this protein. The aims of this study were to characterize the distribution of CAV1 in normal breast, benign breast lesions, breast cancer precursors, and metaplastic breast carcinomas; to assess the prognostic significance of CAV1 expression in invasive breast carcinomas; and to define whether CAV1 gene amplification is the underlying genetic mechanism driving CAV1 overexpression in breast carcinomas. EXPERIMENTAL DESIGN: CAV1 distribution in frozen and paraffin-embedded whole tissue sections of normal breast was evaluated using immunohistochemistry, immunofluorescence, and immunoelectron microscopy. CAV1 expression was immunohistochemically analyzed in benign lesions, breast cancer precursors, and metaplastic breast carcinomas and in a cohort of 245 invasive breast carcinomas from patients treated with surgery followed by anthracycline-based chemotherapy. In 25 cases, CAV1 gene amplification was assessed by chromogenic in situ hybridization. RESULTS: In normal breast, CAV1 was expressed in myoepithelial cells, endothelial cells, and a subset of fibroblasts. Luminal epithelial cells showed negligible staining. CAV1 was expressed in 90% of 39 metaplastic breast carcinomas and in 9.4% of 245 invasive breast cancers. In the later cohort, CAV1 expression was significantly associated with 'basal-like' immunophenotype and with shorter disease-free and overall survival on univariate analysis. CAV1 gene amplification was found in 13% of cases with strong CAV1 expression. CONCLUSIONS: The concurrent CAV1 amplification and overexpression call into question its tumor-suppressive effects in basal-like breast carcinomas.

Breast↗

PubMed2007

A randomized, double-blind, crossover trial of modafinil on mood.

Modafinil, a medication for the excessive sleepiness associated with narcolepsy, has been hypothesized to improve not just alertness but mood as well. The purpose of this study was to determine how treatment with modafinil affects mood in healthy volunteers. Normal healthy volunteers (n = 12, 10 men and 2 women; 30-44 years) underwent a 3-day, counterbalanced, randomized, crossover, inpatient trial of modafinil (400 mg daily) versus placebo with 4-day washout period between 2 treatments. Mood was assessed daily using both the Positive and Negative Affect Schedule and a general mood scale, which consisted of 10 bipolar adjective ratings based on a severity scale ranging from 1 to 10. Modafinil increased general mood and Negative Affect scales relative to placebo and had a significant effect on Positive Affect scales. These results suggest that modafinil may have general mood-elevating effects accompanied by increased negative affect (anxiety). The findings may have implications for clinical practice, in particular for the adjunctive use of modafinil in treatment-resistant depression.

Administration, Oral↗

PubMed2006

Dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland.

The role of estrogen in promoting mammary stem cell proliferation remains controversial. It is unclear if estrogen receptor (ER)-expressing cells have stem/progenitor activity themselves or if they act in a paracrine fashion to stimulate stem cell proliferation. We have used flow cytometry to prospectively isolate mouse mammary ER-expressing epithelial cells and shown, using analysis of gene expression patterns and cell type-specific markers, that they form a distinct luminal epithelial cell subpopulation that expresses not only the ER but also the progesterone and prolactin receptors. Furthermore, we have used an in vivo functional transplantation assay to directly demonstrate that the ER-expressing luminal epithelial subpopulation contains little in vivo stem cell activity. Rather, the mammary stem cell activity is found within the basal mammary epithelial cell population. Therefore, ER-expressing cells of the mammary epithelium are distinct from the mammary stem cell population, and the effects of estrogen on mammary stem cells are likely to be mediated indirectly. These results are important for our understanding of cellular responses to hormonal stimulation in the normal breast and in breast cancer.

AC133 Antigen↗

PubMed2006

Human cerebral autoregulation before, during and after spaceflight.

Exposure to microgravity alters the distribution of body fluids and the degree of distension of cranial blood vessels, and these changes in turn may provoke structural remodelling and altered cerebral autoregulation. Impaired cerebral autoregulation has been documented following weightlessness simulated by head-down bed rest in humans, and is proposed as a mechanism responsible for postspaceflight orthostatic intolerance. In this study, we tested the hypothesis that spaceflight impairs cerebral autoregulation. We studied six astronauts approximately 72 and 23 days before, after 1 and 2 weeks in space (n = 4), on landing day, and 1 day after the 16 day Neurolab space shuttle mission. Beat-by-beat changes of photoplethysmographic mean arterial pressure and transcranial Doppler middle cerebral artery blood flow velocity were measured during 5 min of spontaneous breathing, 30 mmHg lower body suction to simulate standing in space, and 10 min of 60 deg passive upright tilt on Earth. Dynamic cerebral autoregulation was quantified by analysis of the transfer function between spontaneous changes of mean arterial pressure and cerebral artery blood flow velocity, in the very low- (0.02-0.07 Hz), low- (0.07-0.20 Hz) and high-frequency (0.20-0.35 Hz) ranges. Resting middle cerebral artery blood flow velocity did not change significantly from preflight values during or after spaceflight. Reductions of cerebral blood flow velocity during lower body suction were significant before spaceflight (P < 0.05, repeated measures ANOVA), but not during or after spaceflight. Absolute and percentage reductions of mean (+/- s.e.m.) cerebral blood flow velocity after 10 min upright tilt were smaller after than before spaceflight (absolute, -4 +/- 3 cm s(-1) after versus -14 +/- 3 cm s(-1) before, P = 0.001; and percentage, -8.0 +/- 4.8% after versus -24.8 +/- 4.4% before, P < 0.05), consistent with improved rather than impaired cerebral blood flow regulation. Low-frequency gain decreased significantly (P < 0.05) by 26, 23 and 27% after 1 and 2 weeks in space and on landing day, respectively, compared with preflight values, which is also consistent with improved autoregulation. We conclude that human cerebral autoregulation is preserved, and possibly even improved, by short-duration spaceflight.

Adaptation, Physiological↗

PubMed2006

A polymorphism in the norepinephrine transporter gene alters promoter activity and is associated with attention-deficit hyperactivity disorder.

The norepinephrine transporter critically regulates both neurotransmission and homeostasis of norepinephrine in the nervous system. In this study, we report a previously uncharacterized and common A/T polymorphism at -3081 upstream of the transcription initiation site of the human norepinephrine transporter gene [solute carrier family 6, member 2 (SLC6A2)]. Using both homologous and heterologous promoter-reporter constructs, we found that the -3081(T) allele significantly decreases promoter function compared with the A allele. Interestingly, this T allele creates a new palindromic E2-box motif that interacts with Slug and Scratch, neural-expressed transcriptional repressors binding to the E2-box motif. We also found that both Slug and Scratch repress the SLC6A2 promoter activity only when it contains the T allele. Finally, we observed a significant association between the -3081(A/T) polymorphism and attention-deficit hyperactivity disorder (ADHD), suggesting that anomalous transcription factor-based repression of SLC6A2 may increase risk for the development of attention-deficit hyperactivity disorder and other neuropsychiatric diseases.

Alleles↗

PubMed2006

Spike detection in human muscle sympathetic nerve activity using the kurtosis of stationary wavelet transform coefficients.

The accurate assessment of autonomic sympathetic function is important in the diagnosis and study of various autonomic and cardiovascular disorders. Sympathetic function in humans can be assessed by recording the muscle sympathetic nerve activity, which is characterized by synchronous neuronal discharges separated by periods of neural silence dominated by colored Gaussian noise. The raw nerve activity is generally rectified, integrated, and quantified using the integrated burst rate or area. We propose an alternative quantification involving spike detection using a two-stage stationary wavelet transform (SWT) de-noising method. The SWT coefficients are first separated into noise-related and burst-related coefficients on the basis of their local kurtosis. The noise-related coefficients are then used to establish a threshold to identify spikes within the bursts. This method demonstrated better detection performance than an unsupervised amplitude discriminator and similar wavelet-based methods when confronted with simulated data of varying burst rate and signal to noise ratio. Additional validation on data acquired during a graded head-up tilt protocol revealed a strong correlation between the mean spike rate and the mean integrate burst rate (r=0.85) and burst area rate (r=0.91). In conclusion, the kurtosis-based wavelet de-noising technique is a potentially useful method of studying sympathetic nerve activity in humans.

Action Potentials↗

PubMed2006

A simplified two-component model of blood pressure fluctuation.

We propose a simple moving-average (MA) model that uses the low-frequency (LF) component of the peroneal muscle sympathetic nerve spike rate (LF(spike rate)) and the high-frequency (HF) component of respiration (HF(Resp)) to describe the LF neurovascular fluctuations and the HF mechanical oscillations in systolic blood pressure (SBP), respectively. This method was validated by data from eight healthy subjects (23-47 yr old, 6 male, 2 female) during a graded tilt (15 degrees increments every 5 min to a 60 degrees angle). The LF component of SBP (LF(SBP)) had a strong baroreflex-mediated feedback correlation with LF(spike rate) (r = -0.69 +/- 0.05) and also a strong feedforward relation to LF(spike rate) [r = 0.58 +/- 0.03 with LF(SBP) delay (tau) = 5.625 +/- 0.15 s]. The HF components of spike rate (HF(spike rate)) and SBP (HF(SBP)) were not significantly correlated. Conversely, HF(Resp) and HF(SBP) were highly correlated (r = -0.79 +/- 0.04), whereas LF(Resp) and LF(SBP) were significantly less correlated (r = 0.45 +/- 0.08). The mean correlation coefficients between the measured and model-predicted LF(SBP) (r = 0.74 +/- 0.03) in the supine position did not change significantly during tilt. The mean correlation between the measured and model-predicted HF(SBP) was 0.89 +/- 0.02 in the supine position. R(2) values for the regression analysis of the model-predicted and measured LF and HF powers indicate that 78 and 91% of the variability in power can be explained by the linear relation of LF(spike rate) to LF(SBP) and HF(Resp) to HF(SBP). We report a simple two-component model using neural sympathetic and mechanical respiratory inputs that can explain the majority of blood pressure fluctuation at rest and during orthostatic stress in healthy subjects.

Adult↗

PubMed2006

Sodium paradoxically reduces the gastropressor response in patients with orthostatic hypotension.

Orthostatic hypotension (OH) can cause syncope that is difficult to treat. We have found that 473 mL (16 oz) of water can increase systolic blood pressure (SBP) by > 30 mm Hg in many OH patients (the gastropressor response). OH patients are routinely advised to increase their sodium intake to augment their blood volume. We tested the hypothesis that the ingestion of salt with water would increase the magnitude of the acute pressor response compared with water alone in patients with OH. Patients with OH (n = 9; female = 5; 65+/-3 years) underwent a randomized crossover trial of drinking water (H2O) and salt water (NaCl-H2O). Noninvasive heart rate and BP were measured with the patient seated for > or = 60 minutes after ingestion. The area under the curve for SBP was greater with H2O than NaCl-H2O for the 30 minutes (714+/-388 mm Hg x min versus 364+/-369 mm Hg x min; P = 0.002) and 60 minutes (1454+/-827 mm Hg x min versus 812+/-734 mm Hg x min; P = 0.048) after ingestion. The increase in SBP with H2O was greater than with NaCl-H2O at 30 minutes (37+/-6 versus 18+/-5 mm Hg; P = 0.006) but not at 60 minutes (17+/-6 versus 10+/-6 mm Hg; P = 0.4). Norepinephrine increased after H2O (P = 0.018) but not after NaCl-H2O (P = 0.195). Both oral water and salt water increase BP in patients with OH. Instead of augmenting the gastropressor response, the additional salt paradoxically attenuates the pressor response to water. These data suggest a potentially important role for gastrointestinal osmolality in the activation of the sympathetic nervous system leading to cardiovascular reflexes responsible for the gastropressor response.

Aged↗

PubMed2006

Beta2-adrenoceptor genotype and function affect hemodynamic profile heterogeneity in postural tachycardia syndrome.

Previous studies suggest that the beta2-adrenoceptor functions abnormally in patients with postural tachycardia syndrome (POTS) and may contribute to their altered hemodynamic profile. To test the hypothesis that the beta2-adrenoceptor response is decreased in POTS, we studied: (1) the arterial vasodilation response to the beta agonist, isoproterenol, and (2) the distribution of common polymorphisms (codons 16 and 27) of the gene coding the receptor (beta2-AR) in a large population with POTS. We measured plasma catecholamines and monitored hemodynamics and changes in forearm and leg blood flow to incremental doses of intraarterial isoproterenol in 9 patients with POTS compared with 8 healthy subjects. For polymorphism assessment we collected DNA from 57 patients with POTS and compared with 67 age-sex matched healthy subjects. Circulating catecholamines were significantly higher in POTS subjects compared with controls. Intrabrachial and intrafemoral isoproterenol infusion elicited a dose-dependent increase in blood flow. In healthy subjects, blood flow increased (mean+/-SEM) 400+/-70% in the forearm and 170+/-40% in the leg, but only 280+/-60% in forearms and 120+/-20% in legs of patients with POTS (ANOVA for both P<0.001). The genotype and allele distributions for codons 16 and 27 beta2-AR variants were not different in the 2 groups. However, the blood pressure and plasma norepinephrine levels diverged in patients according to their genotype. Patients with Gly16Gly and patients with Glu27Glu had lower plasma catecholamines and higher supine and upright blood pressure, compared with other genotypes. Therefore, both decreased beta2-adrenoceptor-related vasodilation and beta2-AR polymorphisms may contribute to the hemodynamic diversity of patients with POTS.

Adrenergic beta-Agonists↗

PubMed2006

Clonidine for the treatment of supine hypertension and pressure natriuresis in autonomic failure.

Patients with autonomic failure are disabled by orthostatic hypotension, which can be worsened by the nighttime pressure natriuresis induced by associated supine hypertension. Several pharmacological agents are available that effectively reduce nighttime hypertension, but none of them prevent pressure natriuresis. Because hypertension of autonomic failure can be driven by residual sympathetic tone, we hypothesized that clonidine would be effective in reducing blood pressure (BP) and nocturnal natriuresis. Therefore, we determined the effect of placebo, 0.1 mg clonidine, and 0.1-mg/h nitroglycerin transdermal patch on supine BP, orthostatic hypotension, and pressure natriuresis in 23 patients with primary autonomic failure and supine hypertension. Medications were given at 8:00 PM, and BP was recorded every 2 hours for 12 hours. The maximal decrease in BP was seen 6 to 8 hours after drug administration and was similar to clonidine and nitroglycerin (-29+/-9 and -30+/-10 mm Hg, respectively), as was the average fall in BP throughout the night. However, only clonidine effectively reduced nocturnal natriuresis (-0.09 mmol/mg Cr; 95% CI, -0.13 to -0.04; P=0.004), but this was not associated with improvement in morning orthostatic hypotension because of a residual hypotensive effect. The decrease in BP induced by clonidine was modestly but significantly correlated with the magnitude of residual sympathetic tone determined in 10 subjects by the fall in BP induced by ganglionic blockade (r=0.66; P=0.043). These results are consistent with residual sympathetic tone contributing to supine hypertension in autonomic failure, which can be targeted with clonidine to decrease BP and nocturnal natriuresis.

Aged↗

PubMed2006

Orthostatic hypertension: when pressor reflexes overcompensate.

Orthostatic hypertension--a rise in blood pressure upon assuming upright posture-is an underappreciated and understudied clinical phenomenon. There is currently no widely agreed-upon definition of clinical orthostatic hypertension, the current definitions being operational within the context of particular studies. The underlying pathophysiology is thought to involve activation of the sympathetic nervous system, but the actual etiology is poorly understood. Orthostatic hypertension is observed in association with a variety of other clinical conditions, including essential hypertension, dysautonomias, and type 2 diabetes mellitus. Orthostatic hypertension has been associated with increased occurrence of silent cerebrovascular ischemia and possibly with neuropathy in type 2 diabetes. So, appreciation of the true incidence of orthostatic hypertension, elucidation of the underlying pathophysiology, and an understanding of potentially effective treatment approaches and their associated risks and benefits might all have major clinical significance. Orthostatic hypertension is an aspect of hypertension that is in need of further focused investigation.

Autonomic Nervous System Diseases↗

PubMed2006

Familial orthostatic tachycardia.

PURPOSE OF REVIEW: Postural tachycardia syndrome is an autonomic disorder primarily of younger women. The patient population is heterogeneous, making diagnosis and treatment a challenge. A mutation in the norepinephrine (noradrenaline) transporter gene prompted further genetic analysis. RECENT FINDINGS: Eleven new mutations were found in the human norepinephrine transporter gene, although none were directly associated with postural tachycardia syndrome. The 5'-flanking -1012C --> T variant of the dopamine beta-hydroxylase gene was slightly increased and protection was associated with a reduced incidence of two mutations in the endothelial nitric oxide synthase gene, and one in endothelin-1. Mutations in other disease-related genes suggest a potential relationship with the pathogenesis of postural tachycardia syndrome. Benign joint hypermobility syndrome, for example, shares similar autonomic symptoms and is linked to a mutation in tenascin-X. Additional genetic findings are discussed as potential contributors to vascular health and neurodegeneration. SUMMARY: Genetic testing can reveal molecular mechanisms of disease and provide an additional strategy for diagnosis and treatment of heterogeneous patient populations such as postural tachycardia syndrome. It is quite likely that the pathogenesis of this disorder will be attributed to numerous genetic mutations, both subtle and overt. Therefore, continued study of the relationships between genotype and phenotype are necessary to better understand this syndrome and others with associated dysautonomia.

Autonomic Nervous System Diseases↗

PubMed2006

Comparison of the frequency and physical nature of the lowest order parasitic mode in single crystal and ceramic 2-2 and 1-3 piezoelectric composite transducers.

This work describes an investigation into the first order parasitic mode (i.e., that closest to the fundamental thickness mode) that can occur in 2-2 and 1-3 thickness drive piezoelectric composite transducers. Specifically, the authors compare the performance of piezoceramic and piezocrystal composites with a common passive phase. A local Lamb wave approach is used to describe the generation of such modes, and the validity of this theory is investigated over the entire volume fraction range. It is shown that, when the parasitic mode is primarily generated by Lamb wave activity in the passive phase, both active materials demonstrate similar behavior. However, at higher volume fractions, the first order mode is related to the lateral resonance of the active material, and quite different behavior may be observed between the two sets of devices. The phase velocity of the parasitic modes in each device configuration was investigated by a combination of experimental measurement on a number of transducers along with simulations using the finite-element code PZFlex. Both 2-2 and 1-3 composites made from the single crystal materials pzn-4.5%pt, pzn-8%pt, and pmn-30%pt were investigated along with composites made from pzt5h ceramic. The PZFlex results are compared with experimental impedance analysis and laser scanning of surface displacement, with good agreement demonstrated. By comparing two very different active materials, additional insight into parasitic resonant activity within composite devices is demonstrated.

Journal Article↗

PubMed2006

The importance of recognizing postural pseudoanemia.

The determination of the packed red cell volume and the hemoglobin level has been paramount for monitoring anemia and blood loss for patients in the hospital setting. Recently, these variables have been studied during various control conditions including changes in posture. It has been found that the hematocrit changes markedly with alteration of body posture, in such a way that shifts of estimated blood volume of 1 pint can commonly be elicited by a simple change of posture from supine to upright or vice versa. Therefore, it is important to recognize that in addition to the numerous pathological conditions that may affect the value of the packed cell volume, certain physiological maneuvers may have an equal impact and may confound the accurate assessment of true pathological changes in these variables. Thus, changes in posture can lead to substantial changes in hematocrit, which may be attributed mistakenly to blood loss or acute anemia and may result in a cascade of unnecessary diagnostic costs. In reality, these changes represent postural pseudoanemia, a normal physiological response to a change in position from standing to lying.

Adult↗

PubMed2005

Dishevelled (Dvl-2) activates canonical Wnt signalling in the absence of cytoplasmic puncta.

Dishevelled family proteins are multidomain intracellular transducers of Wnt signals. Ectopically expressed mammalian Dishevelled 2 (Dvl-2) activates downstream signalling and localises to cytoplasmic puncta. It has been suggested that these Dvl-2-containing structures correspond to intracellular vesicles and may be involved in the Wnt signal transduction process. We report that cytoplasmic puncta are primarily formed in cells expressing Dvl-2 at high levels. Lower levels of expression can activate signalling without forming puncta. The structures do not localise with markers of the early or late endocytic pathway and time-lapse analysis demonstrates that Dvl-2 puncta move in a random fashion over short distances but do not originate from the plasma membrane. Based on our findings, we propose that Dvl-2 puncta are protein aggregates that are not required for signalling.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Endothelial NO synthase polymorphisms and postural tachycardia syndrome.

Postural tachycardia syndrome (POTS) is a heterogeneous disorder characterized by an excessive rise in heart rate and symptoms consistent with cerebral hypoperfusion in the upright position. NO produced by endothelial NO synthase is a significant factor in the regulation of blood flow. Genetic polymorphisms in the promoter region (T-786C) and exon 7 (E298D) of the NO synthase isoform 3 gene affect enzyme activity and have been associated with a number of cardiovascular diseases. Because some findings in POTS suggest aberrant NO-mediated functions, we postulated that the variant genotypes of these polymorphisms may increase the risk of developing POTS and correlate with more severe symptoms. We genotyped 136 patients with POTS (mean age 32.2+/-9.9 years; 46 men and 90 women) from Nashville, Tenn, and Vienna, Austria, and compared them with 191 healthy volunteers (mean age 29.1+/-8.0 years; 127 men and 64 women). Participants also underwent orthostatic testing with blood pressure, heart rate, and plasma norepinephrine measurements while supine and upright. The frequencies of the -786CC and 298DD genotypes were significantly lower in patients with POTS than in control subjects (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.14 to 0.57; P=0.001 for -786CC; and OR, 0.44; 95% CI, 0.21 to 0.91; P=0.033 for 298DD). According to 2-locus genotype analyses, patients with -786CC and 298EE or 298ED experienced the largest changes in heart rate and plasma norepinephrine with standing. These results indicate that NO may influence the development of POTS and the severity of POTS symptoms.

Adolescent↗

PubMed2005

Tyramine-induced vasodilation mediated by dopamine contamination: a paradox resolved.

We reported previously that intravenous administration of tyramine induced a paradoxical forearm vasodilation and an increase in plasma dopamine, raising the possibility that dopamine is released by or converted from tyramine in vivo. Alternatively, tyramine can be nonenzymatically oxidized into dopamine in vitro, and this contamination may be responsible for the increase in plasma dopamine and forearm vasodilation. To distinguish between these possibilities, we measured the hemodynamic and neurohumoral effects of an intravenous infusion of a specially prepared dopamine-free tyramine solution in 8 normal volunteers at a dose that increased systolic blood pressure by approximately 25 mm Hg (from 107+/-5 to 133+/-5 mm Hg; P <0.001) and compared it with an equivalent dose of norepinephrine. Tyramine increased plasma norepinephrine (139+/-18 to 226+/-30 pg/mL; P <0.02), its intraneuronal metabolite dihydroxyphenylglycol (980+/-73 to 2245+/-206 pg/mL; P <0.001), and systemic vascular resistance, but not plasma dopamine or its intraneuronal metabolite dihydroxyphenylacetic acid. Tyramine and norepinephrine produced nonsignificant increases in forearm vascular resistance. We conclude that tyramine-induced forearm vasodilation reported in previous studies is explained by the presence of dopamine contamination in tyramine preparations. Intravenous administration of dopamine-free tyramine and norepinephrine produced equivalent systemic vasoconstriction. The forearm vasculature was not useful in monitoring the vasoconstrictive effects of either agent. The possibility of dopamine contamination needs to be considered when interpreting previously published studies using tyramine as a pharmacological tool to assess sympathetic function, and it must be avoided in future studies.

Adult↗