Ana o 3-specific IgE is a good predictor for clinically relevant cashew allergy in children.

INTRODUCTION: Component-resolved diagnostics using specific IgE to 2 S albumins has shown to be a valuable new option in diagnostic procedure. Ana o 3 is a 2 S albumin from cashew. The aim of this study was to investigate the role of Ana o 3-specific serum IgE in the diagnosis of cashew allergy and to identify cut-off levels to replace oral food challenges. Moreover, the value of additional determination of total IgE has been investigated. METHODS: In a multicentre study, we analysed specific IgE to cashew extract and Ana o 3 as well as total IgE in children with suspected cashew allergy using the ImmunoCAP-FEIA and a standardized diagnostic procedure including oral challenges where indicated. RESULTS: A total of 61 patients were included in the study. Forty-two were allergic to cashew, and 19 were tolerant. In receiver operating curves, Ana o 3 discriminates between allergic and tolerant children better than cashew-specific IgE with an area under the curve of 0.94 vs 0.78. The ratio of Ana o 3-specific IgE to total IgE did not further improve the diagnostic procedure. Probability curves for Ana o 3-specific IgE have been calculated, and a 95% probability could be estimated at 2.0 kU/l. CONCLUSION: Specific IgE to Ana o 3 is a valuable tool for the diagnosis of cashew allergy. Considering its positive predictive value, it might allow to make a considerable number of oral challenges superfluous.

Intercellular ultrafast Ca(2+) wave in vascular smooth muscle cells: numerical and experimental study.

Vascular smooth muscle cells exhibit intercellular Ca(2+) waves in response to local mechanical or KCl stimulation. Recently, a new type of intercellular Ca(2+) wave was observed in vitro in a linear arrangement of smooth muscle cells. The intercellular wave was denominated ultrafast Ca(2+) wave and it was suggested to be the result of the interplay between membrane potential and Ca(2+) dynamics which depended on influx of extracellular Ca(2+), cell membrane depolarization and its intercel- lular propagation. In the present study we measured experimentally the conduction velocity of the membrane depolarization and performed simulations of the ultrafast Ca(2+) wave along coupled smooth muscle cells. Numerical results reproduced a wide spectrum of experimental observations, including Ca(2+) wave velocity, electrotonic membrane depolarization along the network, effects of inhibitors and independence of the Ca(2+) wave speed on the intracellular stores. The numerical data also provided new physiological insights suggesting ranges of crucial model parameters that may be altered experimentally and that could significantly affect wave kinetics allowing the modulation of the wave characteristics experimentally. Numerical and experimental results supported the hypothesis that the propagation of membrane depolarization acts as an intercellular messenger mediating intercellular ultrafast Ca(2+) waves in smooth muscle cells.

[Patient Satisfaction after Pitch Elevation and Development of a Therapy Algorithm]. / Zufriedenheit nach Stimmerhöhung bei Transsexualität ­ Entwicklung eines Therapiealgorithmus.

Objective: Voice feminization is an important step in the therapy of male-to-female transsexualism. Approaches are conservative voice therapy and surgical interventions. The most powerful parameter of gender perception is the fundamental frequency. Besides the vocal pitch, there are other parameters influencing gender perception of a voice, e. g. intonation, prosody or formant frequencies. Material and methods: In 21 male to female transgender persons after surgical elevation of the vocal pitch the Voice Handicap Index (VHI), the Life Satisfaction Questionnaire (FLZ) and a new addendum were used. A new algorithm for voice feminization in male-to-female transsexualism was deduced. Results: After elevation of the vocal pitch, the self-confidence of the male-to-female transgender persons has increased. Despite of an elevated pitch some persons were not satisfied with their voice. Conclusion: Surgical intervention changes only the pitch of a voice. To change other parameters, conservative voice therapy is necessary. If the transgender persons are able to reach a satisfying female voice with conservative voice therapy alone, surgical intervention is not indicated.

Self-reported physical activity is associated with cognitive function in lean, but not obese individuals.

Convergent evidence demonstrates that greater physical activity is associated with better cognitive functioning across many patient and healthy samples. However, this relationship has not been well examined among obese individuals and remains unclear. The present study examined the relationship between performance-based measures of attention/executive function and self-reported physical activity, as measured by the International Physical Activity Questionnaire, among lean (n = 36) and obese (n = 36) college students. Lean individuals performed better than obese individuals on measures of attention/executive function. No significant differences in self-reported physical activity emerged between weight groups. Higher self-reported physical activity was related to faster reaction time in lean individuals but slower reaction time in obese individuals. Additionally, in lean individuals, higher levels of self-reported physical activity were related to more errors on a task of speeded inhibitory control. The results are consistent with previous research demonstrating that greater physical activity is associated with faster attention and executive function abilities in healthy samples and highlight the importance of examining reaction time and accuracy indices separately on these measures. The lack of association among obese individuals may be due in part to inaccurate self-report in the current study. Additionally, the cognitive consequences of obesity may outweigh the benefits of physical activity in this group. Future work should investigate these associations in obese individuals using physical activity interventions, as well as a combination of self-report and objective measures to investigate discrepancies in reporting.

Antibodies to phosphatidylserine/prothrombin complex in suspected antiphospholipid syndrome in the absence of antibodies to cardiolipin or Beta-2-glycoprotein I.

Antibodies to phosphatidylserine/prothrombin (aPS/PT) complex were measured in 728 serum specimens from patients suspected of having antiphospholipid syndrome (APS), but without diagnostic elevations in the levels of antibodies to cardiolipin or Beta-2 Glycoprotein 1 (ß2-GP1). Of the 728 specimens, 41 had elevated levels of aPS/PT. Thrombotic events occurred in 11 of the 22 patients with accessible medical histories. Six of the patients with accessible medical records also had laboratory evidence of the lupus anticoagulant. The identification of aPS/PT in patients without evidence of antibodies to cardiolipin, ß2-GP1, or the lupus anticoagulant can contribute to the identification of APS in patients that may go undetected with current testing methods.

An actin length threshold regulates adhesion maturation at the lamellipodium/lamellum interface.

The mechanical coupling between adherent cells and their substrates is a major driver of downstream behavior. This coupling relies on the formation of adhesion sites and actin bundles. How cells generate these elements remains only partly understood. A potentially important mechanism, the length threshold maturation (LTM), has previously been proposed to regulate adhesion maturation and actin bundle stabilization tangential to the leading edge. The LTM describes the process by which cells integrate lamellar myosin forces to trigger adhesion maturation. These forces, cumulated over the length of an actin bundle, are balanced at the anchoring focal complexes. When the bundle length exceeds a certain threshold, the distributed lamellar forces become sufficient to trigger the stabilization of the bundle and its adhesions. In this continuing study, we experimentally challenge the LTM for the first time, by seeding cells on micropatterned substrates with various non-adhesive gaps designed to selectively trigger the LTM. While stable actin bundles were observed on all patterns, their lengths were almost exclusively above 3 µm or 4 µm depending on the cell type. Furthermore, the frequency with which gaps were bridged increased nearly as a step function with increasing gap width, indicating a substrate dependent behavioral switch. These combined observations point strongly to LTM with a threshold above 3 µm. We thus experimentally confirm with two cell types our previous theoretical work postulating the existence of a length dependent threshold mechanism that triggers adhesion maturation and actin bundle stabilization.

The influence of enamel matrix derivative on the angiogenic activity of primary endothelial cells.

BACKGROUND AND OBJECTIVE: Angiogenesis plays a crucial role in early wound healing and tissue regeneration. Although enamel matrix derivative (EMD) has demonstrated the potential to stimulate periodontal regeneration, the biological effects of EMD on angiogenesis and underlying mechanisms have not been fully elucidated. The aim of the present study was to examine the angiogenic effects of EMD in vitro. MATERIAL AND METHODS: Human umbilical vein endothelial cells (HUVECs) were used to assess the effect of EMD on proliferation, survival, adhesion and migration. The effect of EMD on HUVEC angiogenesis was assessed by a three-dimensional sprouting assay. In order to understand the signalling mechanism of altered cell proliferation of HUVECs caused by EMD, the phosphorylation status of ERK1/2 and of the serine/threonine protein kinase Akt was analysed by western blot using phospho-specific antibodies. RESULTS: The proliferation of HUVECs was stimulated by 50 µg/mL EMD, whereas higher concentrations (≥100 µg/mL) resulted in an increased apoptotic rate. The mitogenic response to EMD was associated with the activation of ERK1/2. Enamel matrix derivative did not affect cell adhesion, but all concentrations of EMD tested (0.1-250 µg/mL) promoted migration of HUVECs. Furthermore, EMD induced capillary-like sprout formation from HUVEC spheroids in a dose-dependent manner. CONCLUSION: Our data indicate that EMD acts as a proangiogenic factor in vitro and, as such, might contribute to periodontal tissue regeneration by stimulation of vessel formation during wound healing.

High-resolution cell outline segmentation and tracking from phase-contrast microscopy images.

Accurate extraction of cell outlines from microscopy images is essential for analysing the dynamics of migrating cells. Phase-contrast microscopy is one of the most common and convenient imaging modalities for observing cell motility because it does not require exogenous labelling and uses only moderate light levels with generally negligible phototoxicity effects. Automatic extraction and tracking of high-resolution cell outlines from phase-contrast images, however, is difficult due to complex and non-uniform edge intensity. We present a novel image-processing method based on refined level-set segmentation for accurate extraction of cell outlines from high-resolution phase-contrast images. The algorithm is validated on synthetic images of defined noise levels and applied to real image sequences of polarizing and persistently migrating keratocyte cells. We demonstrate that the algorithm is able to reliably reveal fine features in the cell edge dynamics.

CO2 Laser (10.6 microm) parameters for caries prevention in dental enamel.

Although CO(2) laser irradiation can decrease enamel demineralisation, it has still not been clarified which laser wavelength and which irradiation conditions represent the optimum parameters for application as preventive treatment. The aim of the present explorative study was to find low-fluence CO(2) laser (lambda = 10.6 microm) parameters resulting in a maximum caries-preventive effect with the least thermal damage. Different laser parameters were systematically evaluated in 3 steps. In the first experiment, 5 fluences of 0.1, 0.3, 0.4, 0.5 and 0.6 J/cm(2), combined with high repetition rates and 10 micros pulse duration, were chosen for the experiments. In a second experiment, the influence of different pulse durations (5, 10, 20, 30 and 50 micros) on the demineralisation of dental enamel was assessed. Finally, 3 different irradiation times (2, 5 and 9 s) were tested in a third experiment. In total, 276 bovine enamel blocks were used for the experiments. An 8-day pH-cycling regime was performed after the laser treatment. Demineralisation was assessed by lesion depth measurements with a polarised light microscope, and morphological changes were assessed with a scanning electron microscope. Irradiation with 0.3 J/cm(2), 5 micros, 226 Hz for 9 s (2,036 overlapping pulses) increased caries resistance by up to 81% compared to the control and was even significantly better than fluoride application (25%, p < 0.0001). Scanning electron microscopy examination did not reveal any obvious damage caused by the laser irradiation.

Stretch-elicited calcium responses in the intact mouse thoracic aorta.

Stretch-elicited intracellular calcium ([Ca(2+)](i)) changes in individual smooth muscle cells in a ring of aorta were measured simultaneously with the force developed by the ring. A phasic increase in [Ca(2+)](i) was observed in 30% of the cells and a sustained one in 10%. Depletion of intracellular calcium store by thapsigargin and caffeine decreased phasic and increased sustained calcium responses. The inhibition of calcium entry either by stretching the aorta in a calcium-free medium or by the inhibition of stretch-activated, non-selective cationic channels by 5 microM GsMtx-4 toxin, decreased the proportion of sustained [Ca(2+)](i) responses but increased transient responses. In this condition, a third of the cells responded to stretch by a bursts of [Ca(2+)](i) spikes. The decrease of calcium influx triggered the generation of burst of calcium spikes after the application of stretch steps to the vascular wall. We conclude that progressive recruitment of smooth muscle cells is the mechanism underlying the force-generating part of the myogenic response. Two types of stretch-elicited calcium responses were observed during the recruitment of the smooth muscle cells. One was a phasic calcium discharge generated by the sarcoplasmic reticulum. The second was a tonic response produced by the activation of the stretch-sensitive cationic channels allowing extracellular Ca(2+) entry.

Intercellular communication: role of gap junctions in establishing the pattern of ATP-elicited Ca2+ oscillations and Ca2+-dependent currents in freshly isolated aortic smooth muscle cells.

Cytosolic-free [Ca2+] was evaluated in freshly dissociated smooth muscle cells from mouse thoracic aorta by the ratio of Fura Red and Fluo 4 emitted fluorescence using confocal microscopy. The role of intercellular communication in forming and shaping ATP-elicited responses was demonstrated. Extracellular ATP (250 microM) elicited [Ca2+]i transient responses, sustained [Ca2+]i rise, periodic [Ca2+]i oscillations and aperiodic repetitive [Ca2+]i transients. Quantity of smooth muscle cells in the preparation responding to ATP with periodical [Ca2+]i oscillations depended on the density of isolated cells on the cover slip. ATP-elicited bursts of [Ca2+]i spikes in 66+/-7% of cells in dense and in 33+/-8.5% of cells in non-dense preparations. The number of cells responding to ATP with bursts of [Ca2+]i spikes decreased from 55+/-5% (n=84) to 14+/-3% (n=141) in dense preparations pretreated with carbenoxolone. Simultaneous measurement of [Ca2+]i and ion currents revealed a correlation between [Ca2+]i and current oscillations. ATP-elicited bursts of current spikes in 76% of cells regrouped in small clusters and in 9% of isolated cells. Clustered cells responding to ATP with current oscillations had higher membrane capacity than clustered cells with transient and sustained ATP-elicited responses. Lucifer Yellow (1% in 130 mM KCl) injected into one of clustered cells was transferred to the neighboring cell only when ATP-elicited oscillations. Fast application of carbenoxolone (100 microM) inhibited ATP (250 microM) elicited Ca2+-dependent current oscillations. Taken together these results suggest that the probability of ATP (250 microM) triggered cytosolic [Ca2+]i oscillations accompanied with K+ and Cl- current oscillations increased with the coupling of smooth muscle cells.

Structural changes in human dental enamel after subablative erbium laser irradiation and its potential use for caries prevention.

Numerous studies have confirmed the potential of erbium laser irradiation for increasing the acid resistance of dental enamel. The objective of the present paper was to investigate the effect of subablative erbium laser irradiation on the structure and acid resistance of dental enamel by means of confocal laser scanning microscopy (CLSM). To this end, 12 samples of human dental enamel were irradiated with subablative energy densities (Phi) of an Er:YAG (lambda = 2.94 microm, Phi = 6 J/cm(2)) and an Er:YSGG laser (lambda = 2.79 microm, Phi = 8 J/cm(2)). The enamel surfaces of 6 samples were polished prior to irradiation. The remaining 6 samples were left intact (without polishing procedures) and, in the further course of the study, they were subjected to 1-week in situ demineralisation. All irradiated test surfaces were assigned a control surface on the same sample. The changes following laser irradiation and the in situ wearing time were assessed qualitatively using a confocal laser scanning microscope. The irradiation of dental enamel with subablative erbium laser irradiation produces fine cracks in the enamel surface. These cracks act as starting points for acid attack and favour deep demineralisation. These changes reduce or eliminate the positive effect of subablative erbium laser irradiation observed in connection with caries-preventive use. The clinical use of subablative erbium laser irradiation to prevent caries would appear not to make sense under the conditions studied.

Model of coupled transient changes of Rac, Rho, adhesions and stress fibers alignment in endothelial cells responding to shear stress.

Interactions of cell adhesions, Rho GTPases and actin in the endothelial cells' response to external forces are complex and not fully understood, but a qualitative understanding of the mechanosensory response begins to emerge. Here, we formulate a mathematical model of the coupled dynamics of cell adhesions, small GTPases Rac and Rho and actin stress fibers guiding a directional reorganization of the actin cytoskeleton. The model is based on the assumptions that the interconnected cytoskeleton transfers the shear force to the adhesion sites, which in turn transduce the force into a chemical signal that activates integrins at the basal surface of the cell. Subsequently, activated and ligated integrins signal and transiently de-activate Rho, causing the disassembly of actin stress fibers and inhibiting the maturation of focal complexes into focal contacts. Focal complexes and ligated integrins activate Rac, which in turn enhances focal complex assembly. When Rho activity recovers, stress fibers re-assemble and promote the maturation of focal complexes into focal contacts. Merging stress fibers self-align, while the elevated level of Rac activity at the downstream edge of the cell is translated into an alignment of the cells and the newly forming stress fibers in the flow direction. Numerical solutions of the model equations predict transient changes in Rac and Rho that compare well with published experimental results. We report quantitative data on early alignment of the stress fibers and its dependence on cell shape that agrees with the model.

The caries-preventive potential of subablative Er:YAG and Er:YSGG laser radiation in an intraoral model: a pilot study.

OBJECTIVE: The aim of the present study was to investigate the effect of sub-ablative Er:YAG and Er:YSGG laser radiation on the demineralization of human dental enamel in situ. METHODS: Eighteen enamel specimens were prepared to this end, nine of which were irradiated at 8 J/cm(2) with the Er:YSGG laser and nine at 6 J/cm(2) with the Er:YAG laser (125 pulses per surface). Each test surface was assigned a control surface on the same specimen. Three healthy volunteers from each group subsequently wore three enamel specimens in situ for a period of 1 week. The demineralization was assessed by determining the surface microhardness according to Knoop (KH) before and after wearing. RESULTS: Before wearing, the mean surface hardness measured on the control surfaces was 233 (SD 99) KH (CYSGG) and 162 (SD 59) KH (CYAG). After sub-ablative laser irradiation, the surface hardness values measured were already found to be lower compared to the untreated control surfaces (YSGG: 195 [SD 110] KH/YAG: 112 [SD 72] KH). Marked demineralization was observed on the control surfaces after 1 week of wearing in situ (CYSGG*: 60 [SD 57] KH; CYAG*: 53 [SD 9] KH). After wearing, the hardness on the irradiated test surfaces was ErYSGG*: 133 [SD 58] KH and ErYAG*: 89 [SD 28] KH, and was thus higher than on the control surfaces. CONCLUSIONS: The results indicate a tendency towards increased caries resistance following sub-ablative erbium laser irradiation. However, in an analysis of variance model with repeated measures, the tendency in this study failed to reach statistical significance (alpha = 0.05).

Myofibroblast development is characterized by specific cell-cell adherens junctions.

Myofibroblasts of wound granulation tissue, in contrast to dermal fibroblasts, join stress fibers at sites of cadherin-type intercellular adherens junctions (AJs). However, the function of myofibroblast AJs, their molecular composition, and the mechanisms of their formation are largely unknown. We demonstrate that fibroblasts change cadherin expression from N-cadherin in early wounds to OB-cadherin in contractile wounds, populated with alpha-smooth muscle actin (alpha-SMA)-positive myofibroblasts. A similar shift occurs during myofibroblast differentiation in culture and seems to be responsible for the homotypic segregation of alpha-SMA-positive and -negative fibroblasts in suspension. AJs of plated myofibroblasts are reinforced by alpha-SMA-mediated contractile activity, resulting in high mechanical resistance as demonstrated by subjecting cell pairs to hydrodynamic forces in a flow chamber. A peptide that inhibits alpha-SMA-mediated contractile force causes the reorganization of large stripe-like AJs to belt-like contacts as shown for enhanced green fluorescent protein-alpha-catenin-transfected cells and is associated with a reduced mechanical resistance. Anti-OB-cadherin but not anti-N-cadherin peptides reduce the contraction of myofibroblast-populated collagen gels, suggesting that AJs are instrumental for myofibroblast contractile activity.

Influence of the spatial beam profile on hard tissue ablation. Part I: Multimode emitting Er:YAG lasers.

Uniform dosimetry is a prerequisite for reproducible laser applications in research and practice. The light-tissue interaction is dependent on the absorbed energy (J) per unit of time (tau) in the case of pulsed lasers, and on the absorbed power (W) per unit of volume (e.g. mm3) in the case of continuous-wave (cw) lasers, and thus directly dependent on the energy distribution within the laser beam. Consequently, precise knowledge of the spatial beam profile, and of the pulse duration and treatment time, is indispensable. The objective of this paper was a theoretical study of the impact of different mode profiles on energy distribution in the beam. Also examined was the question of the influence of changes in the laser parameters on the mode structure. Three erbium:YAG lasers (lambda=2.94 microm) were used for this purpose. The transversal mode structure of the lasers was observed by irradiating thermal paper and verified by means of calculations. The effect induced in the mode profile by changing the pulse energy and pulse repetition rate was investigated. The results of the tests show that changes in the laser parameters result in jumps in the transversal modes and associated energy distributions in the beam. The experiments confirm that simply changing the transversal modes has a substantial effect on the threshold energy required for the ablation of dental enamel (50 mJ with TEM00, 22.6 mJ with TEM31). In practice, inhomogeneity makes it impossible to determine the irradiated area in order to calculate the energy or power density. In addition, the energy distribution in the beam changes as a result of variation of the laser output energy and the pulse repetition rate. Consequently, simply measuring the beam diameter yields a totally incorrect result for the applied flux density when using a beam profile with a relatively high mode.

Analysis of actin dynamics at the leading edge of crawling cells: implications for the shape of keratocyte lamellipodia.

Leading edge protrusion is one of the critical events in the cell motility cycle and it is believed to be driven by the assembly of the actin network. The concept of dendritic nucleation of actin filaments provides a basis for understanding the organization and dynamics of the actin network at the molecular level. At a larger scale, the dynamic geometry of the cell edge has been described in terms of the graded radial extension model, but this level of description has not yet been linked to the molecular dynamics. Here, we measure the graded distribution of actin filament density along the leading edge of fish epidermal keratocytes. We develop a mathematical model relating dendritic nucleation to the long-range actin distribution and the shape of the leading edge. In this model, a steady-state graded actin distribution evolves as a result of branching, growth and capping of actin filaments in a finite area of the leading edge. We model the shape of the leading edge as a product of the extension of the actin network, which depends on actin filament density. The feedback between the actin density and edge shape in the model results in a cell shape and an actin distribution similar to those experimentally observed. Thus, we explain the stability of the keratocyte shape in terms of the self-organization of the branching actin network.

The ablation threshold of Er:YAG and Er:YSGG laser radiation in dental enamel.

The scientific investigation of fundamental problems plays a decisive role in understanding the mode of action and the consequences of the use of lasers on biological material. One of these fundamental aspects is the investigation of the ablation threshold of various laser wavelengths in dental enamel. Knowledge of the relationships and influencing factors in the laser ablation of hard tooth tissue constitutes the basis for use in patients and the introduction of new indications. The present paper examines the ablation threshold of an Er:YAG laser (lambda=2.94 micro m) and an Er:YSGG laser (lambda=2.79 micro m) in human dental enamel. To this end, 130 enamel samples were taken from wisdom teeth and treated with increasing energy densities of 2-40 J/cm(2). The sample material was mounted and irradiated on an automated linear micropositioner. Treatment was performed with a pulse duration of tau(P(FWHM)) approximately 150 micro s and a pulse repetition rate of 5 Hz for both wavelengths. The repetition rate of the laser and the feed rate of the micropositioner resulted in overlapping of the single pulses. The surface changes were assessed by means of reflected light and scanning electron microscopy. On the basis of the results, it was possible to identify an energy density range as the ablation threshold for both the Er:YAG and the Er:YSGG laser. With the Er:YAG laser, the transition was found in an energy density range of 9-11 J/cm(2). The range for the Er:YSGG laser was slightly higher at 10-14 J/cm(2).

Influence of the pulse duration of an Er:YAG laser system on the ablation threshold of dental enamel.

The present study examines the dependence of the ablation threshold on the duration of the applied laser pulses in the dental enamel of human wisdom teeth. To this end, 600 treatments with the Er:YAG laser (lambda=2940 nm) were carried out on a total of 50 extracted teeth. The laser light was coupled into a fluoride glass light guide for this purpose, in order to ensure almost gaussian distribution of the light in a radially symmetrical beam. The beam diameter on the specimen was 610 micro m. The radiant exposure on the tooth surface was varied between 2 and 20 J/cm(2), while the duration of the pulses applied was changed in four steps from 100 micro s to 700 micro s. The irradiated tooth surfaces were examined for visible signs of ablation under a reflected-light microscope. The experiments revealed that, when pulses of shorter duration are used, the limit at which ablation sets in is reduced by up to approx. 3 J/cm(2). This expands the ablation threshold range of Er:YAG laser radiation to between 6 and 10 J/cm(2). In this context, both the pulse duration and the radiant exposure have a statistically significant influence on the ablation threshold (logistic regression, p<0.0001). Although the ablation threshold of the dental enamel can be changed by varying the pulse duration of the Er:YAG laser, no clinical consequences can be expected, as the shift is only slight.

Adaptation of conduit artery vascular smooth muscle tone to induced hypertension.

We studied the changes in vascular smooth muscle (VSM) cell tone during the adaptation of rat common carotids to induced hypertension. Hypertension was induced in 8 week old male Wistar rats by total ligation of the aorta between the two kidneys. Mean blood pressure increased abruptly from 92 +/- 2mm Hg (mean +/- SE) to 145 +/- 4 mm Hg and remained constant thereafter. Rats were sacrificed 2, 4, 8, and 56 days after surgery and the left common carotid artery was excised for analysis. Pressure-diameter curves were measured in vitro under normal, maximally contracted, and totally relaxed VSM. The VSM tone was analyzed in terms of its basal tone (active stress at low strains) and its myogenic tone (increase in active stress at high strains). Our results show that the capacity of the VSM to develop maximal active stress is not altered in hypertension. Basal tone, however, increases rapidly in the acute hypertension phase (2-8 days postsurgery) and drops to nearly control values at 56 days postsurgery. Also, the onset of myogenic response decreases to lower strains following the step change in pressure, to be restored back to control levels at 56 days postsurgery. We conclude that VSM adaptation is most significant in the acute hypertension phase and acts as a first, rapid defense mechanism for the arterial wall. The VSM tone returns back to normal levels once the slower geometrical and structural remodeling is developed sufficiently to restore the biomechanical environment and function of the arterial wall to control levels.