Prevalence of variants in methylenetetrahydrofolate reductase and the severity of pulmonary vascular disease.

Pulmonary hypertension is a serious disease associated with constriction, cellular proliferation, inflammation, and in situ thrombosis of the small vessels of the lung. Some studies suggest that homozygous 677TT variants and compound heterozygous 677CT/1298AC variants in methylenetetrahydrofolate reductase may increase the risk for systemic vascular disease. We sought to determine the prevalence of variants in methylenetetrahydrofolate reductase in patients with pulmonary hypertension, and whether homozygous or compound heterozygous variants are associated with an increased severity of disease. The medical records of patients with pulmonary hypertension were retrospectively reviewed to identify 105 patients who were evaluated for variants in methylenetetrahydrofolate reductase. The frequency of the minor allele 677C > T was 0.352 and the frequency of the minor allele 1298A > C was 0.295. The number of patients who were homozygous 677TT, homozygous 1298CC or compound heterozygous 677CT/1298AC was similar to the number of control patients with corresponding variants in a meta-analysis of studies. Patients with homozygous or compound heterozygous variants had a significantly higher ratio of pulmonary to systemic vascular resistance (0.75 ± 0.07 vs. 0.56 ± 0.04, p = 0.019) during baseline heart catheterization. Twenty-five of 61 patients without, and 28 of 44 patients with, homozygous or compound heterozygous variants had moderate to severe disease (p = 0.030). Variants in methylenetetrahydrofolate reductase are common in the general population and in patients with pulmonary hypertension. It is unlikely that these variants cause pulmonary vascular disease; however, they may influence the progression or severity of disease.

Tibial and femoral articular cartilage exhibit opposite outcomes for T1ρ and T2* relaxation times in response to acute compressive loading in healthy knees.

Abnormal loading is thought to play a key role in the disease progression of cartilage, but our understanding of how cartilage compositional measurements respond to acute compressive loading in-vivo is limited. Ten healthy subjects were scanned at two timepoints (7 ± 3 days apart) with a 3 T magnetic resonance imaging (MRI) scanner. Scanning sessions included T1ρ and T2* acquisitions of each knee in two conditions: unloaded (traditional MRI setup) and loaded in compression at 40 % bodyweight as applied by an MRI-compatible loading device. T1ρ and T2* parameters were quantified for contacting cartilage (tibial and femoral) and non-contacting cartilage (posterior femoral condyle) regions. Significant effects of load were found in contacting regions for both T1ρ and T2*. The effect of load (loaded minus unloaded) in femoral contacting regions ranged from 4.1 to 6.9 ms for T1ρ, and 3.5 to 13.7 ms for T2*, whereas tibial contacting regions ranged from -5.6 to -1.7 ms for T1ρ, and -2.1 to 0.7 ms for T2*. Notably, the responses to load in the femoral and tibial cartilage revealed opposite effects. No significant differences were found in response to load between the two visits. This is the first study that analyzed the effects of acute loading on T1ρ and T2* measurements in human femoral and tibial cartilage separately. The results suggest the effect of acute compressive loading on T1ρ and T2* was: 1) opposite in the femoral and tibial cartilage; 2) larger in contacting regions than in non-contacting regions of the femoral cartilage; and 3) not different visit-to-visit.

In situ microindentation for determining local subchondral bone compressive modulus.

Alterations to joint tissues, including subchondral bone, occur with osteoarthritis. A microindentation technique was developed to determine the local compressive modulus of subchondral bone. This test, in conjunction with a cartilage indentation test at the same location, could evaluate changes of these material properties in both tissues. The accuracy of the technique was determined by applying it to materials of known moduli. The technique was then applied to rat tibial plateaus to characterize the local moduli of the subchondral bone. An established nanoindentation method was adopted to determine the modulus of subchondral bone following penetration of the overlying articular cartilage. Three cycles of repeated loadings were applied (2.452 N, 30 s hold). The slope of the load-displacement response during the unloading portion of the third cycle was used to measure the stiffness. Indentation tests were performed on two polyurethane foams and polymethyl-methacrylate for validation (n=15). Regression analysis was used to compare the moduli with reference values. Subchondral bone moduli of tibial plateaus from Sprague-Dawley rats (n=5) were measured for central and posterior locations of medial and lateral compartments. An analysis of variance was used to analyze the effects of compartment and test location. The measured moduli of the validation materials correlated with the reference values (R(2)=0.993, p=0.05). In rat tibial plateaus, the modulus of the posterior location was significantly greater than the center location (4.03+/-1.00 GPa and 3.35+/-1.16 GPa respectively, p=0.03). The medial compartment was not different from the lateral compartment. This method for measuring the subchondral bone in the same location as articular cartilage allows studies of the changes in these material properties with the onset and progression of osteoarthritis.

CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis.

Centromere protein-F (CENP-F) is mammalian kinetochore protein that was recently identified by an autoimmune serum (Rattner, J. B., A. Rao, M. J. Fritzler, D. W. Valencia, and T. J. Yen. Cell Motil. Cytoskeleton. 26:214-226). We report here the human cDNA sequence of CENP-F, along with its expression and localization patterns at different stages of the HeLa cell cycle. CENP-F is protein of the nuclear matrix that gradually accumulates during the cell cycle until it reaches peak levels in G2 and M phase cells and is rapidly degraded upon completion of mitosis. CENP-F is first detected at the prekinetochore complex during late G2, and is clearly detectable as paired foci that correspond to all the centromeres by prophase. During mitosis, CENP-F is associated with kinetochores from prometaphase until early anaphase and is then detected at the spindle midzone throughout the remainder of anaphase. By telophase, CENP-F is concentrated within the intracellular bridge at either side of the mid-body. The predicted structure of the 367-kD CENP-F protein consists of two 1,600-amino acid-long coil domains that flank a central flexible core. A putative P-loop nucleotide binding site (ADIPTGKT) is located within the globular carboxy terminus. The structural features deduced from our sequence studies and the spatial and temperal distribution of CENP-F revealed in our cytological and biochemical studies suggest that it may play a role in several mitotic events.

Radiographic-based measurement of tibiofemoral joint space width and magnetic resonance imaging derived articular cartilage thickness are not related in subjects at risk for post traumatic arthritis of the knee.

Joint space width (JSW), measured as the distance between the femoral and tibial subchondral bone margins on two-dimensional weight-bearing radiographs, is the initial imaging modality used in clinical settings to diagnose and evaluate the progression of osteoarthritis (OA). While, JSW is the only structural outcome approved by the FDA for studying the treatment of this disease in phase III clinical trials, recent reports suggest that magnetic resonance imaging (MRI)-based measurements of OA changes are superior due to increased sensitivity and specificity to the structural changes associated with progression of this disease. In the current study, we examined the relationship between radiographic JSW and MRI-derived articular cartilage thickness in subjects 4 years post anterior cruciate ligament reconstruction (ACLR) who were at increased risk for the onset and early progression of post-traumatic OA, and in uninjured subjects with normal knees (Control). In both ACLR and Control groups, there were large measurement biases, wide limits of agreement, and poor correlation between the two measurement techniques. Clinical significance: The finding from this study suggest that the two methods of examining changes associated with the onset and early progression of PTOA either characterize different structures about the knee and should not be used interchangeably, or two-dimensional JSW measurements are not sensitive to small changes in articular cartilage thickness. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Risk Factors Associated With a Noncontact Anterior Cruciate Ligament Injury to the Contralateral Knee After Unilateral Anterior Cruciate Ligament Injury in High School and College Female Athletes: A Prospective Study.

BACKGROUND: The incidence of contralateral anterior cruciate ligament (CACL) injuries after recovery from a first-time anterior cruciate ligament (ACL) disruption is high in women; however, little is known about the risk factors associated with this trauma. HYPOTHESIS: Patient characteristics, strength, anatomic alignment, and neuromuscular characteristics of the contralateral uninjured leg at the time of the first ACL trauma are associated with risk of subsequent CACL injury, and these risk factors are distinct from those for a first-time ACL injury. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Sixty-one women who suffered a first-time noncontact ACL injury while participating in high school or college sports and underwent measurement of potential risk factors on their contralateral limb soon after the initial ACL injury and before reconstruction were followed until either a CACL injury or an ACL graft injury occurred, or until the last date of contact. RESULTS: Follow-up information was available for 55 (90.0%) of the 61 athletes and 11 (20.0%) suffered a CACL injury. Younger age, decreased participation in sport before the first ACL disruption, decreased anterior stiffness of the contralateral knee, and increased hip anteversion were associated with increases in the risk of suffering a CACL injury. CONCLUSION: A portion of CACL injury risk factors were modifiable (time spent participating in sport and increasing anterior knee stiffness with bracing), while others were nonmodifiable (younger age and increased hip anteversion). The relationship between younger age at the time of an initial ACL injury and increased risk of subsequent CACL trauma may be explained by younger athletes having more years available to be exposed to at-risk activities compared with older athletes. A decrease of anterior stiffness of the knee is linked to decreased material properties and width of the ACL, and this may explain why some women are predisposed to bilateral ACL trauma while others only suffer the index injury. The risk factors for CACL injury are unique to women who suffer bilateral ACL trauma compared with those who suffer unilateral ACL trauma. This information is important for the identification of athletes who may benefit from risk reduction interventions.

Analyzing 3-tesla magnetic resonance imaging units for implementation in radiosurgery.

OBJECT: The limiting factor affecting accuracy during gamma knife surgery is image quality. The new generation of magnetic resonance (MR) imaging units with field strength up to 3 teslas promise superior image quality for anatomical resolution and contrast. There are, however, questions about chemical shifts or susceptibility effects, which are the subject of this paper. METHODS: The 3-tesla MR imaging unit (Siemens Trio) was analyzed and compared with a 1-tesla unit (Siemens Magnetom Expert) and to a 1.5-tesla unit (Philips Gyroscan). Evaluation of the magnitude of error was performed within transverse slices in two orientations (axial/coronal) by using a cylindrical phantom with an embedded grid. Deviations were determined for 21 targets in a slab phantom with known geometrical positions within the stereotactic frame. Distortions caused by chemical shift and/or susceptibility effects were analyzed in a head phantom. Inhouse software was used for data analyses. The mean deviation was less than 0.3 mm in axial and less than 0.4 mm in coronal orientations. For the known targets the maximum deviation was 1.16 mm. By optimizing these parameters in the protocol these inaccuracies could be reduced to less than 1.1 mm. Due to inhomogeneities a shift in the z direction of up to 1.5 mm was observed for a dataset, which was shown to be compressed by 1.2 mm. CONCLUSIONS: The 3-tesla imaging unit showed superior anatomical contrast and resolution in comparison with the established 1-tesla and 1.5-tesla units; however, due to the high field strength the field within the head coil is very sensitive to inhomogeneities and therefore 3-tesla imaging data will have be handled with care.

Corrections to universal fluctuations in correlated systems: the two-dimensional XY model.

Generalized universality, as recently proposed, postulates a universal non-Gaussian form of the probability density function (PDF) of certain global observables for a wide class of highly correlated systems of finite volume N. Studying the two-dimensional XY model, we link its validity to renormalization group properties. It would be valid if there were a single dimension 0 operator, but the actual existence of several such operators leads to T-dependent corrections. The PDF is the Fourier transform of the partition function Z(q) of an auxiliary theory which differs by a dimension 0 perturbation with a very small imaginary coefficient iq/N from a theory which is asymptotically free in the infrared. We compute the PDF from a systematic loop expansion of ln Z(q).

Combined anatomic factors predicting risk of anterior cruciate ligament injury for males and females.

BACKGROUND: Knee joint geometry has been associated with risk of suffering an anterior cruciate ligament (ACL) injury; however, few studies have utilized multivariate analysis to investigate how different aspects of knee joint geometry combine to influence ACL injury risk. HYPOTHESES: Combinations of knee geometry measurements are more highly associated with the risk of suffering a noncontact ACL injury than individual measurements, and the most predictive combinations of measurements are different for males and females. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total of 88 first-time, noncontact, grade III ACL-injured subjects and 88 uninjured matched-control subjects were recruited, and magnetic resonance imaging data were acquired. The geometry of the tibial plateau subchondral bone, articular cartilage, and meniscus; geometry of the tibial spines; and size of the femoral intercondylar notch and ACL were measured. Multivariate conditional logistic regression was used to develop risk models for ACL injury in females and males separately. RESULTS: For females, the best fitting model included width of the femoral notch at its anterior outlet and the posterior-inferior-directed slope of the lateral compartment articular cartilage surface, where a millimeter decrease in notch width and a degree increase in slope were independently associated with a 50% and 32% increase in risk of ACL injury, respectively. For males, a model that included ACL volume and the lateral compartment posterior meniscus to subchondral bone wedge angle was most highly associated with risk of ACL injury, where a 0.1 cm3 decrease in ACL volume (approximately 8% of the mean value) and a degree decrease in meniscus wedge angle were independently associated with a 43% and 23% increase in risk, correspondingly. CONCLUSION: Combinations of knee joint geometry measurements provided more information about the risk of noncontact ACL injury than individual measures, and the aspects of geometry that best explained the relationship between knee geometry and the risk of injury were different between males and females. Consequently, a female with both a decreased femoral notch width and an increased posterior-inferior-directed lateral compartment tibial articular cartilage slope combined or a male with a decreased ACL volume and decreased lateral compartment posterior meniscus angle were most at risk for sustaining an ACL injury.

Exacerbation of Gilles de la Tourette's syndrome associated with thermal stress: a family study.

Gilles de la Tourette's syndrome (TS) is a familial disorder that is often exacerbated by stress or fatigue. Here we present a family of a TS proband that has several members with obsessive-compulsive symptoms, a bleeding disorder, and an unusual sensitivity to heat. The proband, who is affected by all of these traits, was challenged with heat or exercise in climate-controlled conditions and showed a marked increase in the frequency of tics.

Third component of rat complement. Purification from plasma and radioimmunoassay in culture media from cell lines.

A double antibody radioimmunoassay for rat C3 has been developed. The assay required the preparation of C3 from plasma. A new purification procedure using ion exchange high performance liquid chromatography is described. The final product was homogeneous on SDS-PAGE analysis. Rat C3 has an apparent molecular weight of 187,000 and is composed of two polypeptide chains with molecular weights of 125,000 and 73,000, respectively. The purified C3 antigen with high hemolytic reactivity, as assessed by its specific functional activity, was used in preparing anti-C3 sera to perform a specific radioimmunoassay for quantifying C3 in the presence of heterologous sera contained in the cell culture media. All the validating criteria, such as precision, recovery and dilution studies, were investigated. The high sensitivity of the method allowed replicate determination of C3 in small aliquots of the cell culture medium.

Computer-assisted liver-mass estimation from gamma-camera images.

We have devised a computer-assisted method for objective estimation of liver mass from the right lateral projection of radiocolloid images of the liver. Gamma-camera images were digitized, preprocessed, and stored in computer memory. The definition of liver for area measurement was adaptively determined by means of a Laplacian operator that measures change in radioactivity slope associated with the liver margin. Individual thresholds were calculated for each of 16 subregions. A liver-mass index was derived from a linear regression model correlating the area of the right lateral projection with liver weight at autopsy in 50 patients whose livers weighed between 0.8 to 3.0 Kg. The correlation coefficient found for this method was 0.83 using the equation: Liver Mass [kg] = Area [cm2]/275 [kg/cm2]--0.215 [kg]. Liver-mass estimates using an alternative computer-assisted method or representative manual methods adapted for gamma-camera images showed lower correlation with liver weight at autopsy.

Diminished venous vascular capacitance in patients with univentricular hearts after the Fontan operation.

Patients who have undergone Fontan's operation are known to have impaired cardiac output response to dynamic exercise. This may be due to either poor cardiac function or a limited ability to mobilize blood from capacitance vessels due to increased resting venous tone. We tested the latter hypothesis by determining venous vascular capacitance at rest and during orthostatic stress produced by lower body negative pressure (LBNP) in 6 subjects who had undergone the Fontan operation and 6 healthy age-, sex-, height-, and weight-matched controls. Resting blood volume was similar for Fontan and control subjects (79 +/- 6 vs 70 +/- 3 ml/kg body weight, respectively), while central venous pressure (CVP) was elevated in Fontan subjects (18.4 +/- 1.0 vs 3.5 +/- 0.9 mm Hg, p < 0.05). Forearm venous capacitance at a distending pressure of 40 mm Hg was less in Fontan subjects than in controls (2.6 +/- 0.1 vs 3.9 +/- 0.5 ml/100 ml), while resting plasma norepinephrine level was elevated in Fontan subjects (255 +/- 28 vs 144 +/- 9 pg/ml, p < 0.05). The increase in calf volume (1.6 +/- 0.2 vs 2.3 +/- 0.2 ml) and decrease in CVP (-5.0 +/- 0.5 vs -6.7 +/- 1.1 mm Hg) during -30 mm Hg LBNP were smaller for Fontan than control subjects (p < 0.05). Reduced forearm venous capacitance and diminished pooling of blood into capacitance vessels of the leg during orthostatic stress indicated higher venous tone in Fontan than control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Monoamine oxidase in rat arteries: evidence for different forms and selective localization.

1. Two forms of monoamine oxidase activity were differentiated in rat mesenteric and femoral artery by means of substrate and inhibitor specificities: one form deaminated tyramine, 5-hydroxytryptamine and noradrenaline and was highly sensitive to pargyline and clorgyline but resistant towards carbonyl reagents. This form resembled type A monoamine oxidase previously described. The other deaminated tyramine but not 5-hydroxytryptamine or noradrenaline and was inhibited by carbonyl reagents but not by clorgyline or pargyline.2. About one third of the total monoamine oxidase in homogenates of rat mesenteric artery was recovered in a 10(5)g supernatant. Both forms were partially soluble, but relatively less of the type A activity was recovered in the soluble fraction.3. Chemical sympathectomy with 6-hydroxydopamine resulted in a loss of 59% of monoamine oxidase activity in the mesenteric artery. There was a selective loss of type A activity, as revealed by the 70% decrease in 5-hydroxytryptamine deaminating ability and by the marked decrease in clorgyline sensitivity. The second monoamine oxidase species was resistant to 6-hydroxydopamine. The soluble activity was not affected by chemical sympathectomy. Most of the transmitter-specific monoamine oxidase of the arterial wall was localized within the adrenergic nerve endings. Our observations are consistent with the hypothesis that extraneuronal monoamine oxidase plays only a minor role in metabolizing noradrenaline in sympathetically innervated tissues.4. Plasma amine oxidase might originate from the arterial wall since it has similar characteristics to that found in the mesenteric artery.

Cholinergic involvement in ethanol intoxication and withdrawal-induced seizure susceptibility.

The enzymes of the cholinergic system have been investigated in discrete brain areas in alcohol-dependent rats, which were still intoxicated or were undergoing withdrawal. The ethanol intoxication resulted in a slight, but significant increase in choline acetyltransferase (CAT) activity in the caudate nucleus both 1 and 7 h after the last dose of ethanol. We also found a significant decrease in CAT activity in the temporal limbic cortex while rats were highly intoxicated. All other brain regions investigated, e.g., cerebellum, pons-medulla, frontoparietal cortex, hypothalamus and septum showed unchanged CAT activity. Rats were also analysed immediately following the onset of a withdrawal-induced audiogenic convulsive seizure where, in addition to the striatum, depressed CAT activity was observed in the hippocampus. In all the analysed situations acetylcholinesterase activity remained unchanged. These results show that ethanol intoxication leads to a perturbation in the synthetic capacity of acetylcholine in certain defined brain structures and that this may have some correlation to the observed behavioural impairments.

Integrating centrosome structure with protein composition and function in animal cells.

The centrosome found in animal cells is a complex and dynamic organelle that functions as the major microtubule organizing center. Structural studies over the past several decades have defined the primary structural features of the centrosome but recent studies are now beginning to reveal structural detail previously unknown. Concurrent with these studies has been an explosion in the identification of the proteins that reside within the centrosome. Our growing understanding of how protein composition integrates with centrosome structure and hence with function is the focus of this review.

Assessment of cutaneous blood flow by using topographical perfusion mapping techniques.

The ability of laser Doppler scanning to reproduce the spatial pattern of cutaneous vascular conductance (CVC) in a 6.25-cm2 area of skin was evaluated at supine rest (28 degrees C), during thermal stress (cold and heat), and during baroreceptor unloading with -40-mmHg lower body negative pressure (LBNP). The spatial pattern of resting CVC was similar on 3 different days, varying by 6 +/- 3%. During cold stress, 89 +/- 2% of the skin area showed a decrease in skin blood flow (37 +/- 2%), whereas heat stress increased CVC in 94 +/- 5% of the skin area. During LBNP, the pattern of CVC response was not uniform, and frequency analysis indicated that 47 +/- 5% of the pixels showed a reduction in CVC (>1 SE), 28 +/- 2% of the skin area were unaffected, and the remaining 26 +/- 5% of the pixels showed some increase in CVC. These data indicate the ability of topographical perfusion mapping to provide quantitative and reproducible information about the spatial distribution of CVC. In addition, the site-to-site variability in reflex control of skin blood flow during LBNP is intriguing and requires more rigorous evaluation.

Effect of lymphatic outflow pressure on lymphatic albumin transport in humans.

The effects of posture on the lymphatic outflow pressure and lymphatic return of albumin were examined in 10 volunteers. Lymph flow was stimulated with a bolus infusion of isotonic saline (0.9%, 12.6 ml/kg body wt) under four separate conditions: upright rest (Up), upright rest with lower body positive pressure (LBPP), supine rest (Sup), and supine rest with lower body negative pressure (LBNP). The increase in plasma albumin content (Delta Alb) during the 2 h after bolus saline infusion was greater in Up than in LBPP: 82.9 +/- 18.5 vs. -28.4 mg/kg body wt. Delta Alb was greater in LBNP than in Sup: 92.6 vs. -22.5 +/- 18.9 mg/kg body wt (P < 0.05). The greater Delta Alb in Up and Sup with LBNP were associated with a lower estimated lymphatic outflow pressure on the basis of the difference in central venous pressure (Delta CVP). During LBPP, CVP was increased compared with Up: 3.8 +/- 1.4 vs. -1.2 +/- 1.2 mmHg. During LBNP, CVP was reduced compared with Sup: -3.0 +/- 2.2 vs. 1.7 +/- 1.0 mmHg. The translocation of protein into the vascular space after bolus saline infusion reflects lymph return of protein and is higher in Up than in Sup. Modulation of CVP with LBPP or LBNP in Up and Sup, respectively, reversed the impact of posture on lymphatic outflow pressure. Thus posture-dependent changes in lymphatic protein transport are modulated by changes in CVP through its mechanical impact on lymphatic outflow pressure.

Reflex control of the cutaneous circulation during passive body core heating in humans.

The impact of body core heating on the interaction between the cutaneous and central circulation during blood pressure challenges was examined in eight adults. Subjects were exposed to -10 to -90 mmHg lower body negative pressure (LBNP) in thermoneutral conditions and -10 to -60 mmHg LBNP during heat stress. We measured forearm vascular conductance (FVC; ml. min(-1). 100 ml(-1). mmHg(-1)) by plethysmography; cutaneous vascular conductance (CVC) by laser-Doppler techniques; and central venous pressure, arterial blood pressure, and cardiac output by impedance cardiography. Heat stress increased FVC from 5.7 +/- 0.9 to 18.8 +/- 1.3 conductance units (CU) and CVC from 0.21 +/- 0.07 to 1.02 +/- 0.20 CU. The FVC-CVP relationship was linear over the entire range of LBNP and was shifted upward during heat stress with a slope increase from 0. 46 +/- 0.10 to 1.57 +/- 0.3 CU/mmHg CVP (P < 0.05). Resting CVP was lower during heat stress (6.3 +/- 0.6 vs. 7.7 +/- 0.6 mmHg; P < 0. 05) but fell to similar levels during LBNP as in normothermic conditions. Data analysis indicates an increased capacity, but not sensitivity, of peripheral baroreflex responses during heat stress. Laser-Doppler techniques detected thermoregulatory responses in the skin, but no significant change in CVC occurred during mild-to-moderate LBNP. Interestingly, very high levels of LBNP produced cutaneous vasodilation in some subjects.

Baroreceptor modulation of active cutaneous vasodilation during dynamic exercise in humans.

The hypothesis that baroreceptor unloading during dynamic limits cutaneous vasodilation by withdrawal of active vasodilator activity was tested in seven human subjects. Increases in forearm skin blood flow (laser-Doppler velocimetry) at skin sites with (control) and without alpha-adrenergic vasoconstrictor activity (vasodilator only) and in arterial blood pressure (noninvasive) were measured and used to calculate cutaneous vascular conductance (CVC). Subjects performed two similar dynamic exercise (119 +/- 8 W) protocols with and without baroreceptor unloading induced by application of -40 mmHg lower body negative pressure (LBNP). The LBNP condition was reversed (i.e., either removed or applied) after 15 min while exercise continued for an additional 15 min. During exercise without LBNP, the increase in body core temperature (esophageal temperature) required to elicit active cutaneous vasodilation averaged 0.25 +/- 0.08 and 0.31 +/- 0.10 degrees C (SE) at control and vasodilator-only skin sites, respectively, and increased to 0.44 +/- 0.10 and 0.50 +/- 0.10 degrees C (P < 0.05 compared with without LBNP) during exercise with LBNP. During exercise baroreceptor unloading delayed the onset of cutaneous vasodilation and limited peak CVC at vasodilator-only skin sites. These data support the hypothesis that during exercise baroreceptor unloading modulates active cutaneous vasodilation.