Changes In Intravascular Pressure Research Articles

Multiple blood flow surges during intermittent pneumatic compression: The origins and their implications

Intermittent pneumatic compression (IPC) therapy has been used to enhance peripheral blood flow for prevention and rehabilitation of ischemic–related vascular diseases. A novel phenomenon has been reported that multiple blood flow surges appeared in the skin blood flow signal during each compression, but its mechanism has not been fully revealed. This study aimed to gain insights into the origins of these blood flow surges through experiment and biomechanical modeling methods. Foot skin blood flow (SBF) signals of 13 healthy adults (23.8 ± 0.5 yr old, 7 males) and air cuff pressure signals were recorded during IPC. Lumped parameter modeling and wavelet analysis were adopted to investigate the multiple blood flow surges (named as Peak1, Peak2 and Peak3). The results of the simulated Peak1 and Peak2 were in good agreements with the experiment results, suggesting that IPC could enhance foot SBF not only by deflation, but also by inflation. Statistical analysis demonstrated that high frequency compression with more frequent occurrence of Peak1 and Peak2 lead to significantly higher (Friedman test, p < 0.001) time–averaged SBF enhancement than the traditional mode. In addition, wavelet analysis showed that the major frequency component of the Peak3 (0.059 Hz) was within the range of the vascular myogenic activity, suggesting a vascular regulation process triggered by intravascular pressure changes. Our study provide new insights into the mechanism of how IPC enhance foot SBF.

Abstract No. 298 Intravascular pressure changes during transarterial embolization therapy in a benchtop hepatic vascular model

Abstract No. 298 Intravascular pressure changes during transarterial embolization therapy in a benchtop hepatic vascular model

TRPV4-dependent signaling mechanisms in systemic and pulmonary vasculature.

The delicate balance between constrictor and dilator mechanisms is a vital determinant of blood pressure and blood flow. The maintenance of this balance requires constant communication between different cell-types in the vascular wall. In this regard, the transient receptor potential vanilloid type 4 (TRPV4) ion channel, a Ca2+-permeable non-selective cation channel, has emerged as a crucial regulator of Ca2+-mediated changes in vascular reactivity. Recent studies suggest that TRPV4 channels regulate vasoconstriction and arterial pressure in the systemic and pulmonary vasculature. New emerging data support a dilatory role of endothelial TRPV4 channels, and both constrictor and dilator roles of smooth muscle TRPV4 channels. Moreover, TRPV4 channel activity has been implicated in physiological functions of vascular support cells, such as fibroblasts and pericytes, to assist the sustenance of vascular reactivity in response to changes in intravascular pressure or external stimulation. Importantly, a growing body of evidence connects abnormal TRPV4 channel activity to multiple vascular disorders. This chapter will review the current literature on the cell-type specific roles of vascular TRPV4 channels in regulating physiological function. Additionally, we summarize our understanding of the contribution of abnormal TRPV4 channel activity to various vascular disorders.

Blunt injury of liver: mechanical response of porcine liver in experimental impact test

Objective. The liver is frequently injured in blunt abdominal trauma caused by road traffic accidents. The testing of safety performance of vehicles, e.g. belt usage, head support, seat shape, or air bag shape, material, pressure and reaction, could lead to reduction of the injury seriousness. Current trends in safety testing include development of accurate computational human body models (HBMs) based on the anatomical, morphological, and mechanical behavior of tissues under high strain. Approach. The aim of this study was to describe the internal pressure changes within porcine liver, the severity of liver injury and the relation between the porcine liver microstructure and rupture propagation in an experimental impact test. Porcine liver specimens (n = 24) were uniformly compressed using a drop tower technique and four impact heights (200, 300, 400 and 500 mm; corresponding velocities: 1.72, 2.17, 2.54 and 2.88 m s−1). The changes in intravascular pressure were measured via catheters placed in portal vein and caudate vena cava. The induced injuries were analyzed on the macroscopic level according to AAST grade and AIS severity. Rupture propagation with respect to liver microstructure was analyzed using stereological methods. Main results. Macroscopic ruptures affected mostly the interface between connective tissue surrounding big vessels and liver parenchyma. Histological analysis revealed that the ruptures avoided reticular fibers and interlobular septa made of connective tissue on the microscopic level. Significance. The present findings can be used for evaluation of HBMs of liver behavior in impact situations.

Invasive Assessment of Hemodynamic, Metabolic and Ionic Consequences During Blood Flow Restriction Training.

Purpose: Medically recommended training often faces the dilemma that necessary mechanical intensities for muscle adaptations exceed patients' physical capacity. In this regard, blood flow restriction (BFR) training is becoming increasingly popular because it enables gains in muscle mass and strength despite using low-mechanical loads combined with external venous occlusion. Since the underlying mechanisms are still unknown, we applied invasive measurements during exercise with and without BFR to promote physiological understanding and safety of this popular training technique.Methods: In a randomized cross-over design, ten healthy men (28.1 ± 6.5 years) underwent two trials of unilateral biceps curls either with (BFR) and without BFR (CON). For analysis of changes in intravascular pressures, blood gases, oximetry and electrolytes, an arterial and a venous catheter were placed at the exercising arm before exercise. Arterial and venous blood gases and intravascular pressures were analyzed before, during and 5 min after exercise.Results: Intravascular pressures in the arterial and venous system were more increased during exercise with BFR compared to CON (p < 0.001). Furthermore, arterial and venous blood gas analyses revealed a BFR-induced metabolic acidosis (p < 0.05) with increased lactate production (p < 0.05) and associated elevations in [K+], [Ca2+] and [Na+] (p < 0.001).Conclusion: The present study describes for the first time the local physiological changes during BFR training. While BFR causes greater hypertension in the arterial and venous system of the exercising extremity, observed electrolyte shifts corroborate a local metabolic acidosis with concurrent rises in [K+] and [Na+]. Although BFR could be a promising new training concept for medical application, its execution is associated with comprehensive physiological challenges.

Regulation of blood flow in small arteries: mechanosensory events underlying myogenic vasoconstriction.

As blood flow is proportional to the fourth power of the vascular radius small changes in the diameter of resistance arteries/arterioles following an increase in intraluminal pressure would be expected to substantially increase blood flow. However, arteriolar myocytes display an intrinsic ability to locally regulate blood flow according to metabolic demands by tuning the diameter of small arteries in response to local changes in he-modynamics. Critical to this, observations were made more than 100 years ago that mechanosensitive small arteries exhibit the “myogenic response” or pressure-induced vasoconstriction or vasodilation in re-sponse to increased or decreased intravascular pressure, respectively. Although cellular mechanisms underlying the myogenic response have now been studied extensively, the precise cellular mechanisms under-lying this intriguing phenomenon still remain uncertain. In particular, the biological machinery that senses changes in intravascular pressure in vascular smooth muscle cells have not been unquestionably identified and remain a significant issue in vascular biology to be fully elucidated. As such, this brief review focuses on putative mechanosensors that have been proposed to contribute to myogenic vasoreactivity. Specific attention is paid to the roles of integrins, G protein-coupled receptors, and cadherins.

Forward blood flow provoked by changing intravascular pressure using an extracorporeal circulation during cardiopulmonary resuscitation

Since both “cardiac pump” and “thoracic pump” theories have been proved during cardiopulmonary resuscitation (CPR), the mechanism of forward blood flow during closed chest compression still remains open to question. The cardiac pump seems to work by the direct compression of the cardiac ventricles between the sternum and vertebral column. A pressure gradient created between the ventricle and aorta generates systemic blood flow. However, the thoracic pump mechanism presumes chest compression causes a rise in intrathoracic pressure which generates a blood flow from the thoracic cavity to the systemic circulation. Retrograde blood flow from the right heart into the systemic veins is prevented by a concomitant collapse of veins at the thoracic inlet. We hypothesize that the intrinsic decrease of vascular resistance from the aorta to peripheral arteries and the existence of competent venous valves enable blood to flow unidirectionally by the fluctuation of intravascular pressures during closed chest compression. The purpose of this study is to prove an antegrade arterial blood flow without cardiac compression and intrathoracic pressure changes in an animal cardiac arrest model. We demonstrate that arterial pulses can be developed by using an extracorporeal circuit, resulting in forward blood flow from the aorta through the systemic vasculature. It can be suggested that changes in intravascular pressure provoked by either cardiac or thoracic pump generate systemic blood flow during closed chest compression, while systemic vascular patency and valve function may be required for successful CPR.

Noninvasive Estimation of Pressure Changes Using 2-D Vector Velocity Ultrasound: An Experimental Study With In Vivo Examples.

A noninvasive method for estimating intravascular pressure changes using 2-D vector velocity is presented. The method was first validated on computational fluid dynamic (CFD) data and with catheter measurements on phantoms. Hereafter, the method was tested in vivo at the carotid bifurcation and at the aortic valve of two healthy volunteers. Ultrasound measurements were performed using the experimental scanner SARUS, in combination with an 8 MHz linear array transducer for experimental scans and a carotid scan, whereas a 3.5-MHz phased array probe was employed for a scan of an aortic valve. Measured 2-D fields of angle-independent vector velocities were obtained using synthetic aperture imaging. Pressure drops from simulated steady flow through six vessel geometries spanning different degrees of diameter narrowing, running from 20%-70%, showed relative biases from 0.35% to 12.06%, depending on the degree of constriction. Phantom measurements were performed on a vessel with the same geometry as the 70% constricted CFD model. The derived pressure drops were compared to pressure drops measured by a clinically used 4F catheter and to a finite-element model. The proposed method showed peak systolic pressure drops of -3 kPa ± 57 Pa, while the catheter and the simulation model showed -5.4 kPa ± 52 Pa and -2.9 kPa, respectively. An in vivo acquisition of 10 s was made at the carotid bifurcation. This produced eight cardiac cycles from where pressure gradients of -227 ± 15 Pa were found. Finally, the aortic valve measurement showed a peak pressure drop of -2.1 kPa over one cardiac cycle. In conclusion, pressure gradients from convective flow changes are detectable using 2-D vector velocity ultrasound.

Membrane potential and Ca2+ concentration dependence on pressure and vasoactive agents in arterial smooth muscle: A model.

Arterial smooth muscle (SM) cells respond autonomously to changes in intravascular pressure, adjusting tension to maintain vessel diameter. The values of membrane potential (Vm) and sarcoplasmic Ca(2+) concentration (Ca(in)) within minutes of a change in pressure are the results of two opposing pathways, both of which use Ca(2+) as a signal. This works because the two Ca(2+)-signaling pathways are confined to distinct microdomains in which the Ca(2+) concentrations needed to activate key channels are transiently higher than Ca(in). A mathematical model of an isolated arterial SM cell is presented that incorporates the two types of microdomains. The first type consists of junctions between cisternae of the peripheral sarcoplasmic reticulum (SR), containing ryanodine receptors (RyRs), and the sarcolemma, containing voltage- and Ca(2+)-activated K(+) (BK) channels. These junctional microdomains promote hyperpolarization, reduced Ca(in), and relaxation. The second type is postulated to form around stretch-activated nonspecific cation channels and neighboring Ca(2+)-activated Cl(-) channels, and promotes the opposite (depolarization, increased Ca(in), and contraction). The model includes three additional compartments: the sarcoplasm, the central SR lumen, and the peripheral SR lumen. It incorporates 37 protein components. In addition to pressure, the model accommodates inputs of α- and β-adrenergic agonists, ATP, 11,12-epoxyeicosatrienoic acid, and nitric oxide (NO). The parameters of the equations were adjusted to obtain a close fit to reported Vm and Ca(in) as functions of pressure, which have been determined in cerebral arteries. The simulations were insensitive to ± 10% changes in most of the parameters. The model also simulated the effects of inhibiting RyR, BK, or voltage-activated Ca(2+) channels on Vm and Ca(in). Deletion of BK β1 subunits is known to increase arterial-SM tension. In the model, deletion of β1 raised Ca(in) at all pressures, and these increases were reversed by NO.

The Gastrointestinal Circulation: Physiology and Pathophysiology.

The gastrointestinal (GI) circulation receives a large fraction of cardiac output and this increases following ingestion of a meal. While blood flow regulation is not the intense phenomenon noted in other vascular beds, the combined responses of blood flow, and capillary oxygen exchange help ensure a level of tissue oxygenation that is commensurate with organ metabolism and function. This is evidenced in the vascular responses of the stomach to increased acid production and in intestine during periods of enhanced nutrient absorption. Complimenting the metabolic vasoregulation is a strong myogenic response that contributes to basal vascular tone and to the responses elicited by changes in intravascular pressure. The GI circulation also contributes to a mucosal defense mechanism that protects against excessive damage to the epithelial lining following ingestion of toxins and/or noxious agents. Profound reductions in GI blood flow are evidenced in certain physiological (strenuous exercise) and pathological (hemorrhage) conditions, while some disease states (e.g., chronic portal hypertension) are associated with a hyperdynamic circulation. The sacrificial nature of GI blood flow is essential for ensuring adequate perfusion of vital organs during periods of whole body stress. The restoration of blood flow (reperfusion) to GI organs following ischemia elicits an exaggerated tissue injury response that reflects the potential of this organ system to generate reactive oxygen species and to mount an inflammatory response. Human and animal studies of inflammatory bowel disease have also revealed a contribution of the vasculature to the initiation and perpetuation of the tissue inflammation and associated injury response.

Cytoskeletal Reorganization Evoked by Rho-associated kinase- and Protein Kinase C-catalyzed Phosphorylation of Cofilin and Heat Shock Protein 27, Respectively, Contributes to Myogenic Constriction of Rat Cerebral Arteries

Our understanding of the molecular events contributing to myogenic control of diameter in cerebral resistance arteries in response to changes in intravascular pressure, a fundamental mechanism regulating blood flow to the brain, is incomplete. Myosin light chain kinase and phosphatase activities are known to be increased and decreased, respectively, to augment phosphorylation of the 20-kDa regulatory light chain subunits (LC20) of myosin II, which permits cross-bridge cycling and force development. Here, we assessed the contribution of dynamic reorganization of the actin cytoskeleton and thin filament regulation to the myogenic response and serotonin-evoked constriction of pressurized rat middle cerebral arteries. Arterial diameter and the levels of phosphorylated LC(20), calponin, caldesmon, cofilin, and HSP27, as well as G-actin content, were determined. A decline in G-actin content was observed following pressurization from 10 mm Hg to between 40 and 120 mm Hg and in three conditions in which myogenic or agonist-evoked constriction occurred in the absence of a detectable change in LC20 phosphorylation. No changes in thin filament protein phosphorylation were evident. Pressurization reduced G-actin content and elevated the levels of cofilin and HSP27 phosphorylation. Inhibitors of Rho-associated kinase and PKC prevented the decline in G-actin; reduced cofilin and HSP27 phosphoprotein content, respectively; and blocked the myogenic response. Furthermore, phosphorylation modulators of HSP27 and cofilin induced significant changes in arterial diameter and G-actin content of myogenically active arteries. Taken together, our findings suggest that dynamic reorganization of the cytoskeleton involving increased actin polymerization in response to Rho-associated kinase and PKC signaling contributes significantly to force generation in myogenic constriction of cerebral resistance arteries.

Original article Disturbed regulation of the isolated middle cerebral artery in acute hyponatremia

Hyponatremia is a common disorder of water-electrolyte balance characterized by the decrease of plasma sodium ions concentration below 135 mM. Although water-electrolyte balance is regulated by a kidney, symptoms of hyponatremia are related to the disturbances of intracranial homeostasis and are attributed to brain swelling. Despite the importance of blood vessels function for the homeostasis of the brain, little is known about the influence of hyponatremia on cerebrovascular regulation. In the present study isolated, perfused and pressurized rat middle cerebral arteries (MCAs) were subjected to hyponatremia in the organ chamber by lowering the concentration of sodium ions from 145 to 121 mM. The response of the MCAs to the changes in intravascular pressure and to endothelium-dependent and independent vasodilators was compared in normo- and hyponatremia. The following results were obtained: the contraction of the MCA during progressive increases in intravascular pressure was similar in normo- and hyponatremia; the dilation in response to acetylcholine (10-6 M, 10-5 M and 10-4 M), which is endothelium- and nitric oxide-dependent, was severely impaired in hyponatremia; the contraction after administration of the nonselective inhibitor of nitric oxide synthesis - NG-nitro-L-arginine methyl ester (L-NAME, 10-5 M) was similar in normo- and hyponatremia; the nitric oxide donor - S-nitroso-N-acetylpenicillamine (SNAP, 10-5 M) dilated MCA only in normonatremia. The results of this study show that myogenic response and shear stress-dependent relaxation of the MCA are not affected by acute hyponatremia. However, agonist-stimulated, endothelial nitric oxide synthase (eNOS)-mediated relaxation is severely impaired which is associated with a decreased smooth muscle response to nitric oxide (NO). In conclusion, our results demonstrate that the regulation of isolated middle cerebral artery is impaired in acute hyponatremia which may contribute to the disturbance of intracranial homeostasis associated with hyponatremia.

Purinergic Receptors Regulate Myogenic Tone in Cerebral Parenchymal Arterioles

Myogenic tone is a fundamental aspect of vascular behavior in resistance arteries. This contractile response to changes in intravascular pressure is critically involved in blood flow autoregulation in tissues such as the brain, kidneys, and heart. Myogenic tone also helps regulate precapillary pressure and provides a level of background tone upon which vasodilator stimuli act to increase tissue perfusion when appropriate. Despite the importance of these processes in the brain, little is known about the mechanisms involved in control of myogenic tone in the cerebral microcirculation. Here, we report that pharmacological inhibition of P2Y4 and P2Y6 pyrimidine receptors nearly abolished myogenic tone in cerebral parenchymal arterioles (PAs). Molecular suppression of either P2Y4 or P2Y6 receptors using antisense oligodeoxynucleotides reduced myogenic tone by 44%±8% and 45%±7%, respectively. These results indicate that both receptor isoforms are activated by increased intravascular pressure, which enhances the activity of voltage-dependent calcium channels and increases myogenic tone in PAs. Enhancement or inhibition of ectonucleotidase activity had no effect on parenchymal arteriolar myogenic tone, indicating that this response is not mediated by local release of nucleotides, but rather may involve direct mechanical activation of P2Y receptors in the smooth muscle cells.

Elevations of local intravascular pressures release vasoactive substances in humans

The wall stiffness of arteries and arterioles adapts to the long-term demands imposed by local intravascular pressure. We investigated whether substances capable of inducing acute and long-term effects on arterial wall stiffness are released locally into the bloodstream in response to an acute marked increase in local intravascular pressure in the blood vessels of the human arm. Experiments were performed on ten subjects positioned in a pressure chamber with one arm extended through a hole in the chamber door and kept at normal atmospheric pressure. Intravascular pressure was increased in the arm, by a stepwise increase in chamber pressure up to +150 mmHg. Diameter and flow were measured in the brachial artery by Doppler ultrasonography. Blood samples were drawn simultaneously from both arms before, during, immediately after and 2 h after the release of the chamber pressure. Plasma levels of endothelin-1 (ET-1), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2) and angiotensin II (Ang-II) were measured. Elevation of chamber pressure by 150 mmHg increased local arterial distending pressure to about 220-260 mmHg, resulting in an increase in brachial artery diameter of 9% and flow of 246%. The pressure stimulus increased the plasma levels of ET-1 and Ang-II, but not of VEGF-A or FGF-2 in the test arm. The local release of the vasoconstrictors ET-1 and Ang-II in response to markedly increased distending pressure may reflect one mechanism behind adaptation to acute and long-term changes in intravascular pressure.

Mysteries in the Local Control of Blood Flow

In mystery writings, the classification of a “whodunit” refers to a story in which the puzzle of who committed the crime is the main feature of interest. In a somewhat comparable manner, interrogations into the local control of blood flow can be construed as chapters of a physiological whodunit mystery—of course, with the hope that the science is nonfictional! For the physiological whodunit, the cast of characters consists of the myriad factors involved in the local control of blood flow, including adenosine, nitric oxide, hydrogen peroxide, and ATP, to name a few. Article, see p 220 The specific factors responsible for the local control of blood flow have eluded unequivocal identification. Perhaps this difficulty relates to the likely possibility that there are redundant local control mechanisms that regulate flow, so that when one system is blocked, another can assume control. Another complication is that local control of flow is related to many different conditions, including changes in tissue oxygen demands, ischemia, hypoxia, changes in intravascular pressure, and changes in shear stresses, and these myriad factors introduce a highly complicated system that likely follows nonlinear dynamics, at least in the heart.1 In this issue of Circulation Research , Kirby et al2 have added a chapter in the whodunit mystery by suggesting that the intravascular production of ATP contributes to dilation in skeletal muscle during systemic hypoxia and active (exercise-induced) hyperemia in humans. The authors further suggest that diminished ATP release by red cells in aged individuals contributes to the hampered vasodilatory responses to hypoxia and increased muscle metabolism observed in older persons. This clinical study appears to be well done, and there appear to be no issues with the results. However, …

Emerging role of G protein-coupled receptors in microvascular myogenic tone

Blood flow autoregulation results from the ability of resistance arteries to reduce or increase their diameters in response to changes in intravascular pressure. The mechanism by which arteries maintain a constant blood flow to organs over a range of pressures relies on this myogenic response, which defines the intrinsic property of the smooth muscle to contract in response to stretch. The resistance to flow created by myogenic tone (MT) prevents tissue damage and allows the maintenance of a constant perfusion, despite fluctuations in arterial pressure. Interventions targeting MT may provide a more rational therapeutic approach in vascular disorders, such as hypertension, vasospasm, chronic heart failure, or diabetes. Despite its early description by Bayliss in 1902, the cellular and molecular mechanisms underlying MT remain poorly understood. We now appreciate that MT requires a complex mechanotransduction converting a physical stimulus (pressure) into a biological response (change in vessel diameter). Although smooth muscle cell depolarization and a rise in intracellular calcium concentration are recognized as cornerstones of the myogenic response, the role of wall strain-induced formation of vasoactive mediators is less well established. The vascular system expresses a large variety of Class 1 G protein-coupled receptors (GPCR) activated by an eclectic range of chemical entities, including peptides, lipids, nucleotides, and amines. These messengers can function in blood vessels as vasoconstrictors. This review focuses on locally generated GPCR agonists and their proposed contributions to MT. Their interplay with pivotal G(q-11) and G(12-13) protein signalling is also discussed.

Role for αvβ3 in the regulation of Ca2+ dynamics and myogenic tone development in rat cerebral arteries

Intravascular pressure induces cerebral arterial tone by augmenting the activity of voltage‐gated Ca2+ channels (VGCC) and the generation of Ca2+ waves from the sarcoplasmic reticulum (SR). The signaling events that enable intravascular pressure to alter cytosolic Ca2+ dynamics and arterial tone remain uncertain. In this study we propose that the αvβ3‐integrin along with the downstream signaling proteins, focal adhesion kinase (FAK) and phospholipase C (PLCγ1), play a central role in the transduction of the myogenic response. In rat cerebral arteries denuded of endothelium, elevated intravascular pressure (20 to 80 mmHg) augmented FAK/PLCγ1 phosphorylation and the mobilization of Ca2+ from the extracellular space and the SR. These changes in cytosolic Ca2+ dynamics influenced the activity of myosin light chain kinase/phosphatase and consequently myogenic tone. Blocking αvβ3 with RGB peptides attenuated FAK/PLCγ1 phosphorylation, Ca2+ mobilization, the activation state of myosin light chain kinase/phosphatase and pressure‐induced tone. PLC inhibition with U73122 initiated a similar attenuating effect. In closing, this study highlights a key role for integrins, FAK and PLC in sensing changes in intravascular pressure, the mobilization of cytosolic Ca2+ and in the development of myogenic tone. Supported by the Natural Science and Engineering Research Council of Canada.

Ca 2+ Sensitization Contributes to Myogenic Control of Arterial Diameter in Skeletal Muscle Resistance Arteries

The myogenic response of resistance arteries to changes in intravascular pressure is a crucial determinant of peripheral vascular resistance. Ca2+ sensitization via inhibition of myosin light chain phosphatase (MLCP), due to phosphorylation of the MLCP targeting subunit 1 (MYPT1) by Rho-associated kinase (ROK), contributes to myogenic constriction of cerebral arteries. As it is unknown if this occurs in non-cerebral vessels we assessed the role of Ca2+ sensitization in the myogenic response of skeletal muscle arterioles (rat gracilis and cremaster). ROK inhibition with H1152 suppressed myogenic constriction between 40 and 120 mmHg. Increasing pressure from 10 to 80 mmHg caused an H1152-sensitive increase in MYPT1-T855 and myosin regulatory light chain (LC20) phosphorylation, but phospho-MYPT1-T697 and -CPI-17 levels were unchanged. Gracilis and cremaster arteries showed high basal levels of LC20 phosphorylation at 10 mmHg, comparable to the level in cerebral arteries at 60 mmHg. These findings suggest that Ca2+ sensitization contributes to the myogenic response of skeletal muscle resistance arteries. High basal LC20 phosphorylation may be the result of increased basal MYPT1 phosphorylation and indicates that myogenic constriction occurs over a narrow range of LC20 phosphorylation. (Support from CIHR MOP-97988 to WCC, AHFMR/CIHR to AEY and Spanish Ministry of Education & Science to OC).

The contribution of arterial versus venous vascular permeability in peritoneal fluid formation

OBJETIVO: o acúmulo de líquido peritoneal é um achado comum em muitas crianças com distúrbios abdominais e sua geração é secundária ao aumento da permeabilidade vascular. A contribuição da circulação arterial versus venosa para a formação de edema e acúmulo de líquido peritoneal é mal compreendida. Estudos realizados in vivo mais de duas décadas atrás, sugeriram que a vênulas são mais importantes que os vasos arteriais no processo de formação de edema. O objetivo deste trabalho é analisar os efeitos das mudanças na pressão intravascular e a inflamação mediada pela bradicinina na permeabilidade venosa e vascular mesentérica de ratos. MÉTODO: artérias mesentéricas (MA) e veias (MV) foram montadas em cânulas de vidro, por via intravenosa preenchida com dextran fluorescentes e incremental pressurizado acima de seus valores fisiológicos in vivo. Permeabilidade vascular para dextrana foi determinada a 100, 200 e 300% de pressões fisiológicas. RESULTADOS: a permeabilidade vascular estava presente em todas as medidas para ambos os vasos e sua magnitude diretamente proporcional à pressão intravascular. A bradicinina (10-5 M) aumentou significativamente a permeabilidade da MV, mas não no MA. CONCLUSÃO: o acúmulo de líquido abdominal relacionado à doença inflamatória intestinal é mais provável de ser secundária a venosa, em oposição à fuga vascular arterial.

Responses of Isolated Pressurised Rat Uterine Arteries to Changes in Pressure: Effects of Pre-constriction, Endothelium and Pregnancy

Pregnancy-induced changes in uterine artery function play a critical role in ensuring adequate placental perfusion. Responses of these vessels to pressure (myogenic responsiveness) may contribute to this. The overall myogenic properties of uterine arteries may depend upon the integration of a number of different factors, including effects of pre-constrictor stimuli, and should be considered in terms of both initial and stable diameters both of which may be modulated by pregnancy. This study thus investigated the effects of pre-constriction, the endothelium and pregnancy on responses of isolated rat uterine arteries to changes in intravascular pressure (IvP). The effects on both the immediate transient diameter changes and stable diameters (myogenic tone) were studied. Isolated 3rd order uterine arteries from non-pregnant and days 19–21 pregnant Sprague–Dawley rats were mounted on a pressure myograph and responses to changes in IvP (20–120mmHg) examined. Arteries did not exhibit active responses to pressure in the absence of stimulation, however, all showed active myogenic constriction when pre-constricted by depolarization (30 or 60mM KCl) or arginine vasopressin (AVP). Pregnancy enhanced stable levels of myogenic tone with AVP, but not depolarization. This difference was not dependent upon the endothelium. Initial peak diameters were enhanced in arteries from pregnant rats due to endothelium-dependent mechanisms. Thus, both the peak and stable response of isolated rat uterine arteries to pressure can be differentially regulated and thus must both be considered when considering the influence of pressure on uterine artery reactivity during pregnancy.