Pressure dependence of superconducting properties of MgB2 /

We prepared samples of MgB2 and ran sets of experiments aimed for investigation of superconducting properties under pressure. We found the value of pressure derivative of the transition temperature -1.2 ± 0.05 K/GPa. Then, using McMillan formula, we found that the main contribution to the change of the transition temperature under the pressure is due to the change in phonon frequencies. Griineisen parameter was calculated to be 7g = 2.4. Our results suggest that MgB2 is a conventional superconductor.

Pressure dependence of superconductivity in amorphous Ni x Zr 100-x alloys

Pressure variations of the superconducting transition temperature Ic of a series of amorphous NixZr 1 OO-x alloys have been studied under quasmydrostatic pressures upto 8 G Pa. For amorphous samples having Ni-concentration less than 40%, i)Tc/dP is positive in sign and it decreases non linearly with increase in I. whereasdTcldP is negative in sign for Ni concentration of 45%. Comparison with the Hall coefficient (I) and the thermoelectric power (2) results for the same amorphous alloys leads to the conclusion that s-d hybridization nature of the d-band (Nil plays a central role in the sign reversal behaviour. Application of pressures greater than 2 G Pa to Ni20ZrgO led to the formation of a new phase, w-Zr. which retains its form after the pressure is released.

Autonomic regulation and blood pressure in children

Vagal baroreflex sensitivity (BRS) is a measure of short term blood pressure (BP) regulation through alterations in heart rate. Low BRS reflects impaired autonomic system regulation and has been found to be a surrogate marker for cardiovascular health. In particular, it has found to be associated with the pathogenesis of adult hypertension. However, only limited information exists as to the negative consequences of childhood BP on baroreflex function. The objective of this study was to investigate BRS in children with 2 different BP profiles while controlling for the effects of age, maturation, sex, and body composition. A preliminary subsample of 11-14 year-old children from the HBEAT (Heart Behavioural Environmental Assessment Team) Study was selected. The children were divided into 2 BP groups; high BP (HBP; 2:95tl1 percentile, n=21) and normal BP (NBP; <90th percentile, n=85). Following an initial 15 minutes of supine rest, 5 minutes of continuous beat-to-beat BP (Finapres) and RR interval (RRI) were recorded (standard ECG). Spectral indices were computed using Fast Fourier Transform and transfer function analysis was used to compute BRS. High frequency (HF) and low frequency (LF) power spectral areas were set to 0.15-0.4 Hz and 0.04-0.15 Hz, respectively. Body composition was measured using body mass index. After adjusting for body composition, maturation, age and sex ANCOV A results were as follows; LF and HF BRS, LF and HF RRI, and RRI total power were lower in the HBP versus NBP participants (p<0.05). As well, LF IHF SBP ratio was significantly higher in the HBP compared to the NBP group (p<0.05). The regression coefficients (unstandardized B) indicated that in changing groups (NBP to HBP) LF and HF BRS decreases by 4.04 and 6.18 ms/mmHg, respectively. Thus, as BP increases, BRS decreases. These data suggest that changes in autonomic activity occur in children who have HBP, regardless of age, sex, maturation, and body composition. Thus, despite their young age and relatively short amount of time having high BP compared with adults, these children are already demonstrating poor BP regulation and reduced cardiovagal activity. Given that childhood BP is associated with hypertension in adulthood, there is a growing concern in regards to the current cardiovascular health of our children and future adults.

The association between blood pressure and vascular characteristics in children

Hypertension is thought to exist in up to five percent of children. A select number of studies have investigated the role elevated blood pressure plays in pediatric atherosclerotic progression. However these studies contain significant methodological flaws and fail to recognize important confounding factors. Therefore, the influence of elevated blood pressure on arterial health in children remains to be clearly understood. The purpose of this study was to investigate the association between blood pressure (BP) and arterial thickness and stiffuess in children. Common carotid artery (CCA) intima-media thickness (IMT) and distensibility (Dist), as well as systemic pulse wave velocity (PWV) were measured in 21 elevated blood pressure (EBP; BP ~ 95th percentile) and 83 normal blood pressure (NBP; BP < 90th percentile) children 11-14 years of age. Both EBP and NBP groups demonstrated BP within the normal clinical range, but EBP showed significantly elevated BP as compared to the NBP group. Independent t-tests failed to show significant differences between the EBP and NBP groups for CCA IMT (0.43 ± 0.05 mm and 0.42 ± 0.06 mm, respectively) and Dist (0.0058 ± 0.0024 mmHg-1 and 0.0064 ± 0.0019 mmHil respectively). In contrast, a significantly elevated PWV (por the effects of maturation, age, sex and obesity. This study shows for the first time that children with elevated BP do not have significantly altered central arterial structure and function as measured through CCA Dist and IMT, but do possess significantly altered systemic arterial stiffuess as measured through PWV. This may be the result of sympathetic predominance and its significant influence on the peripheral vasculature. More studies are needed to clearly illustrate the temporal sequence of pediatric atherosclerotic progression in response to elevated BP.

Retrospective on the Experience of Parental Pressure and Support by Male Participants that Withdrew from Competitive Youth Hockey: A Phenomenological Investigation

The purpose of this study was to gain an in-depth understanding of the lived experiences of parental pressure and support for males who withdrew from competitive youth hockey. A phenomenological approach was used to explore this phenomenon and develop meaning from the participants' experiences. Data for this study was collected by conducting one in-depth interview with each of the seven participants. Fourteen themes emerged as a result of the data analysis. These themes were grouped into three clusters: (1) Description of parental involvement: “I want them to be there and help me”; (2) Perceived impacts of parental involvement: “I felt like he actually cared”; and (3) Impact of parental involvement on commitment: “I kind of miss hockey now”. The descriptions provided by the participants in this study, and the themes that emerged, offer insight into what it is like for young males to experience parental involvement in competitive youth hockey.

Letter - Andrew Cowan to William Cowan

A letter from Andrew Cowan to his son William Cowan 29 Septemer 1841. The letter reads "Dear William, I have taken my pen the third time since I have received any word from you, my first letter was about the beginning of the year, and the second in the month of April with John Armstrong of Northhouse, he sailed from Liverpool the fifteen of that month with his sisters Jane and Jenny and their two children. I received a letter from him dated Cleavland in the State of Ohio the 6 of June. He did not intend stopping in that place. The leaves us all well for any thing that I know, but I have not heard from Andrew since March altho I have writen to him three months since your Mother and I are both sore faild altho we have tolerable good health for which we desire to be thankfull to the giver of all our mercies, which are new every day, that we may be found in Christs and clothed in his imputed righteousness at the last, for in him is only found true happyness. We have had another cold wet Summer and the crops is far back ------ not light, the price of -----is high and trade bad, but sheep and cattle are high. Cattle have not been higher since the French war, but the cattle trade is very bad at present and the opperatives out of imployment and consequently verrry badly of. If none of my former letters have reached you this will inform you that James is at Lanshawburn, and gets imployment all the year, he keeps a cow and five or six sheep, they have three children, Mary, Hannah, and Andrew; I was there after clipping time seeing them, they seem to be verry happy. James Lamb is well he was here the other night, he has got two letters from his son Adam this Summer; they are still in the same place and will finish their job this fall, and seem to be doing well, your Uncle Adam Scott and family are well. John was there lately there is little prospect of his getting to America as the money that was left him is not got yet and will not for some time, If ever this reach you, you must let us know how all the Scotch people that are near you, that went from this place of the Country are doing, as their freinds are anxious to hear from them, perticularly if you know what is becomed of Alexander Hoggs widow and family of ------hill, as I was desired to write to you about them - I got a letter from John Miller dated Gatt but I understand it is a long way from your place he was a gentleman and had the charge of a farm and seems verry ----- Now William if this ever reach you, you must excuse me for not filling this letter up, but if I receive an answer I promise to fill the next better, We all join in our love and respect to you and family. From your loving Father Andrew Cowan

The Effects of Magnetic Dilution and Applied Pressure on Several Frustrated Spinels

The effects of magnetic dilution and applied pressure on frustrated spinels GeNi2O4, GeCo2O4, and NiAl2O4 are reported. Dilution was achieved by substitution of Mg2+ in place of magnetically active Co2+ and Ni2+ ions. Large values of the percolation thresholds were found in GeNi(2-x)MgxO4. Specifically, pc1 = 0.74 and pc2 = 0.65 in the sub-networks associated with the triangular and kagome planes, respectively. This anomalous behaviour may be explained by the kagome and triangular planes behaving as coupled networks, also know as a network of networks. In simulations of coupled lattices that form a network of networks, similar anomalous percolation threshold values have been found. In addition, at dilution levels above x=0.30, there is a T^2 dependency in the magnetic heat capacity which may indicate two dimensional spin glass behaviour. Applied pressures in the range of 0 GPa to 1.2 GPa yield a slight decrease in ordering temperature for both the kagome and triangular planes. In GeCo(2-x)MgxO4, the long range magnetic order is more robust with a percolation threshold of pc=0.448. Similar to diluted nickel germanate, at low temperatures, a T^2 magnetic heat capacity contribution is present which indicates a shift from a 3D ordered state to a 2D spin glass state in the presence of increased dilution. Dynamic magnetic susceptibility data indicate a change from canonical spin glass to a cluster glass behaviour. In addition, there is a non-linear increase in ordering temperature with applied pressure in the range P = 0 to 1.0 GPa. A spin glass ground state was observed in Ni(1-x)MgxAl2O4 for (x=0 to 0.375). Analysis of dynamic magnetic susceptibility data yield a characteristic time of tau* = 1.0x10^(-13) s, which is indicative of canonical spin glass behaviour. This is further corroborated by the linear behaviour of the magnetic specific heat contribution. However, the increasing frequency dependence of the freezing temperature suggests a trend towards spin cluster glass formation.

Sleep bruxism is associated with a rise in blood pressure

Objectifs : Le bruxisme survenant au cours du sommeil est un trouble du mouvement caractérisé par du grincement de dents et l’activité rythmique des muscles masticateurs (ARMM). Le bruxisme/ARMM est souvent associé à des mouvements du corps et des à éveils corticaux. Une séquence d’activation précède le ARMM/bruxisme. Ces événements incluent une augmentation des variables suivants : l’activité sympathique (-4 minutes), les activités encéphalographique (-4 second), le fréquence cardiaque, l’amplitude de la respiration (-1 second) et l’activité des muscle suprahyoïdiens (-0.8 second). La présente étude a examiné l’association entre le bruxisme et les changements de la pression artérielle. Méthodes: Dix sujets avec le bruxisme (5 hommes, 5 femmes, âge moyen = 26 ± 1,8) ont complétés 3 nuits de polysomnographie qui comprenait l'enregistrement non invasive de la pression artérielle. La première nuit a servi de dépistage et d’habituation au laboratoire. L'analyse a été réalisée sur les deuxièmes et troisièmes nuits enregistrements. Seuls les épisodes de bruxisme isolés survenant au cours du stade 2 du sommeil ont été utilisés pour l’analyse, pour un total de 65 épisodes. Les mesures des pressions systolique et diastolique ont été prises 20 battements avant et 23 battements après l'apparition de chaque épisode bruxisme lors du sommeil. Les épisodes de bruxisme ont été classés comme suit: 1) bruxisme avec éveil cortical; 2) bruxisme avec mouvement du corps (MC), 3) bruxisme avec éveil cortical et MC. Une quatrième catégorie, bruxisme seul, a également été analysée, mais utilisée comme donnée préliminaire puisque la catégorie se composait de seulement 4 épisodes de bruxisme. Résultats: Les deux pressions systolique et diastolique ont augmenté avec les épisodes de bruxisme. Cette augmentation a été statistiquement significative pour la pression systolique et diastolique pour les épisodes de bruxisme avec éveil cortical et/ou MC (p ≤ 0,05). L’augmentation moyenne de la pression (systolique / diastolique ± SE) a été : 28,4 ± 2,4/13,2 ± 1,5 mm Hg pour le bruxisme avec éveil cortical; 30,7 ± 1,6/19.4 ± 2.3 mm Hg pour bruxisme avec MC; 26.4 ± 2,8 / 14,6 ± 2.0mm Hg pour bruxisme avec éveil cortical et MC; 22,9 ± 5,2/12,4 ± 3,3mm Hg pour les épisodes de bruxisme seuls. Conclusion: Le bruxisme du sommeil est associé à des hausses de la pression artérielle pendant le sommeil. Cette hausse est supérieure dans les épisodes de bruxisme associés à un éveil cortical et / ou MC, qui sont souvent associés avec les événements bruxisme. Ces résultats sont en accord avec nos observations antérieures, où le bruxisme est précédé par une augmentation de l'activité sympathique et de la tachycardie sinusale.

Contribution of tachykinin and kinin receptors in central autonomic control of blood pressure and behavioural activity in hypertensive rats

This work aims at studing the role of tachykinin NK-3 receptor (R) and kinin B1R in central autonomic regulation of blood pressure (BP) and to determine whether the B1R is overexpressed and functional in rat models of hypertension by measuring the effect of a B1R agonist on behavioural activity. Assumptions: (1) NK-3R located in the ventral tegmental area (VTA) modulates the mesolimbic dopaminergic system and has a tonic activity in hypertension; (2) B1R is overexpressed in the brain of hypertensive rats and has a tonic activity, which contributes to hypertension via a dopamine mechanism; (3) the inhibition of NK-3R and B1R with selective antagonists, reduces central dopaminergic hyperactivity and reverses hypertension. A model of genetic hypertension and a model of experimental hypertension were used: spontaneously hypertensive rats (SHR, 16 weeks) and Wistar-Kyoto (WKY) rats infused for 14 days with angiotensin II (Ang II) (200 ng / kg / min, subcutaneous (s.c.) with Alzet mini pump). The age-matched untreated WKY rats served as common controls. In the first study (article # 1), the cardiovascular response in SHR was evaluated following intracebroventricular (i.c.v.) and/or intra-VTA injection of an agonist (senktide) and antagonists (SB222200 and R-820) of NK-3R. These responses have also been characterized using selective dopamine antagonists DA-D1R (SCH23390), DA-D2R (raclopride) or non-selective dopamine DA-D2R (haloperidol). Also the VTA has been destroyed by ibotenic acid. The pressor response induced by senktide and the anti-hypertensive response induced by SB222200 or R-820 were more pronounced by intra-VTA. These responses were prevented by pre-treatment with raclopride and haloperidol. The lesion of the VTA has prevented the pressor response relayed by senktide (i.c.v.) and the anti-hypertensive effect of R-820 (i.c.v.). In addition, SB222200 (intra-VTA) prevented the pressor response of senktide (i.c.v.) and conversely, senktide (i.c.v.) prevented the antihypertensive effect of SB222200 (intra-VTA). The second study (article # 2) showed that the B1R antagonist (SSR240612) administered by gavage or i.c.v. reverses hypertension in both models. This anti-hypertensive effect was prevented by raclopride and haloperidol. In contrast, the two B1R antagonists (R-715 and R-954) injected s.c., which do not cross the blood-brain barrier reduced weakly blood pressure in hypertensive rats. In the third study (article # 3), the i.c.v. injection of a selective kinin B1R agonist Sar[DPhe8][des-Arg9]BK caused behavioural responses in SHR and Ang II-treated rats and had no effect in control WKY rats . The responses elicited by B1R agonist were blocked by an antagonist of NK-1 (RP67580), an antagonist of NMDA glutamate receptor (DL-AP5), an inhibitor of nitric oxide synthase (NOS) (L -NNA) as well as raclopride and SCH23390.The responses were modestly affected by the inhibitor of inducible NOS (iNOS). The B1R mRNA (measured by RT-PCR) was significantly increased in the hypothalamus, the VTA and the nucleus accumbens of hypertensive animals (SHR and treated with Ang II) compared with control rats. These neuropharmacological studies suggest that: (1) the NK-3R from the VTA is involved in the maintenance of hypertension in SHR by increasing DA transmission in the midbrain; (2) the B1R in SHR and Ang II-treated rats contributes to hypertension via a central mechanism involving DA-D2R; (3) the central B1R increases locomotor activity and nocifensive behaviours via the release of substance P (NK-1), DA and nitric oxide in both rat models of hypertension. Thus, the brain tachykinin NK-3R and kinin B1R represent potential therapeutic targets for the treatment of hypertension. The modulation of the mesolimbic/mesocortical dopaminergic pathway by these receptors suggests their involvement in other physiological functions (pleasure, motor activity, coordination of the response to stress) and pathophysiology (anxiety, depression).

Pro-fibrotic role of ERK3-MK5 during pressure-overload induced cardiac hypertrophy

Il y a 4 isoforme de p38 : α, β, δ, and γ. MK5, à l'origine identifié comme étant un régulateur de PRAK (Regulated/Activated Protein Kinase), est maintenant connu pour être activée par la protéine kinase p38 (qui est un mitogène activé par la protéine kinase, MAPK). Cette dernière est impliquée dans les mécanismes de fibrose et d'apoptose pendant l'hypertrophie cardiaque. De plus, MK5 est également activée par les MAPKs atypiques; ERK3 et ERK4. Bien qu’elles soient fortement exprimées dans le coeur, le rôle physiologique de MK5 et ERK3 demeure inconnu. Par conséquent, nous avons étudié l'effet de la constriction aortique transversale (TAC) – induisant un surcharge chronique de pression chez les souris hétèrozygotes knockout pour MK5 (MK5+/-) ou ERK3 (ERK3+/-) et pour leurs types sauvages (MK5+/+ et ERK3+/+). Deux sem post-TAC; le ratio de poids du coeur/poids corporel a été augmenté chez les 2 souris MK5+/- et MK5+/+. L'échocardiographie de la trans-thoracique démontre que la surcharge de pression a altéré la fonction diastolique du ventricule gauche chez MK5+/+, mais pas chez la souris MK5+/-. De plus, nous avons observé moins de dépôt de collagène, évalué par une coloration au trichrome de Masson, 2 et 3 sem post-TAC chez les souris MK5+/-. Parallèlement, le niveau de l’ARNm de collagène type1 alpha-1 a été significativement diminué dans les coeurs des souris MK5+/-, 2 et 3 sem post-TAC. De même, ERK3, mais pas ERK5 ni p38α, co-IP avec MK5 dans les 2 modèles des coeurs TAC; aigus ou chroniques. En revanche, l’ajout exogénique de GST-MK5 a abaissé ERK4 et p38α, mais pas ERK3 dans les lysâtes de coeur de souris. Par contre, GST-ERK3 et GST-p38α ne démontrent aucune co-IP avec MK5. Ces données suggèrent que dans le coeur seul ERK3, et non ERK4 ou p38α, est capable d’interagir avec, et réguler MK5. A niveau physiologique MK5 interagit entièrement avec ERK3 et par conséquent MK5 n’est pas disponible pour lier les protéines exogéniques. Les souris hétérozygotes pour ERK3 (ERK3+/-) ont également démontré une réduction ou une absence de collagène et une faible expression d’ARNm du collagène type1 alpha1, 3 sem post-TAC. Ces résultats démontrent un important rôle pro-fibrotique de la signalisation MK5-ERK3 pendant une surcharge chronique de pression.Nous avons également démontré 5 variant d'épissage de (MK5.1-5), y compris la forme originale (MK5.1). MK5.2 et MK5.5 subissent une délétion de 6 paires de base dans l’exon 12 : MK5.3 manque l'exon 12 : MK5.4 et MK5.5 manquent les exons 2-6. L'expression des ARNm des différents variant d'épissage a été vérifiée par PCR en temps réel (qPCR). Bien que l’expression est ubiquitaire, l'abondance relative de chaque variant était tissu-spécifique (coeur, rein, pancréas, muscle squelettique, poumon, foie, et cerveau). En plus, l'abondance relative des variant d’épissage varie pendant la surcharge de pression et le développement postnatal du coeur. En outre, l'immunofluorescence a indiqué que MK5.1-5.3 se localise au noyau alors que MK5.4-5.5 est situé au niveau cytoplasmic dans les cellules HEK 293 non stimulées. Suite à une stimulation avec l'anisomycin, un activateur de p38 MAPK, MK5.1-5.3 se translocalise du noyau au cytoplasme alors qu’une petite fraction de MK5.4-5.5 translocalise vers le noyau. Ces variant d'épissage peuvent diversifier la signalisation de MK5-ERK3 dans coeur, mais leur rôle exact oblige des recherches supplémentaires. Excepté l’isoforme δ, toutes les isoformes de p38 sont exprimées dans le coeur et la forme α est considérée comme étant l'isoforme dominante. L’analyse par qPCR et immunobuvardage de type western ont démontré que p38α et p38γ sont les deux isoformes prédominantes alors que p38β et p38δ sont exprimées aux mêmes niveaux dans le coeur de rat adulte. L'immunofluorescence a démontré que p38α et p38γ se trouvent dans le cytoplasme et le noyau. Cependant, suite à la surcharge par TAC, p38γ s'est accumulé dans noyau tandis que la distribution de p38α est demeurée inchangée. Ainsi, l'abondance de p38γ et sa translocalisation nucléaire suite à la surcharge de pression indique un rôle potentiel dans l'expression génique pendant le remodelage cardiaque. En conclusion, nous avons mis en évidence pour la première fois un rôle pro-fibrotique pour la signalisation MK5-ERK3 pendant une surcharge chronique de pression. D'ailleurs, les niveaux comparables d'expression de p38γ avec p38α, et la localisation différentielle de p38γ pendant la surcharge aiguë ou chronique de pression suggèrent différents rôles possibles pour ces isoformes pendant le remodelage hypertrophique cardiaque.

Vascular and morphological changes of the optic nerve head following therapeutic intraocular pressure reduction in open angle glaucoma and ocular hypertension

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

A study of rat chromosome 8 by congenics : Mapping and dissecting quantitative trait loci into opposite blood pressure effects

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Effect of albumin dialysis on intracranial pressure increase in pigs with acute liver failure: a randomized study.

BACKGROUND: Increased intracranial pressure (ICP) worsens the outcome of acute liver failure (ALF). This study investigates the underlying pathophysiological mechanisms and evaluates the therapeutic effect of albumin dialysis in ALF with use of the Molecular Adsorbents Recirculating System without hemofiltration/dialysis (modified, M-MARS). METHODS: Pigs were randomized into three groups: sham, ALF, and ALF + M-MARS. ALF was induced by hepatic devascularization (time = 0). M-MARS began at time = 2 and ended with the experiment at time = 6. ICP, arterial ammonia, brain water, cerebral blood flow (CBF), and plasma inflammatory markers were measured. RESULTS: ICP and arterial ammonia increased significantly over 6 hrs in the ALF group, in comparison with the sham group. M-MARS attenuated (did not normalize) the increased ICP in the ALF group, whereas arterial ammonia was unaltered by M-MARS. Brain water in the frontal cortex (grey matter) and in the subcortical white matter at 6 hrs was significantly higher in the ALF group than in the sham group. M-MARS prevented a rise in water content, but only in white matter. CBF and inflammatory mediators remained unchanged in all groups. CONCLUSION: The initial development of cerebral edema and increased ICP occurs independently of CBF changes in this noninflammatory model of ALF. Factor(s) other than or in addition to hyperammonemia are important, however, and may be more amenable to alteration by albumin dialysis.

Increased extracellular brain glutamate in acute liver failure: decreased uptake or increased release?

Glutamatergic dysfunction has been suggested to play an important role in the pathogenesis of hepatic encephalopathy (HE) in acute liver failure (ALF). Increased extracellular brain glutamate concentrations have consistently been described in different experimental animal models of ALF and in patients with increased intracranial pressure due to ALF. High brain ammonia levels remain the leading candidate in the pathogenesis of HE in ALF and studies have demonstrated a correlation between ammonia and increased concentrations of extracellular brain glutamate both clinically and in experimental animal models of ALE Inhibition of glutamate uptake or increased glutamate release from neurons and/or astrocytes could cause an increase in extracellular glutamate. This review analyses the effect of ammonia on glutamate release from (and uptake into) both neurons and astrocytes and how these pathophysiological mechanisms may be involved in the pathogenesis of HE in ALF.

The role of EphB6 and ephrinbs in blood pressure regulation

L’hypertension artérielle est le facteur de risque le plus important dans les maladies cardiovasculaires (MCV) et les accidents vasculaires cérébraux (AVC). L’hypertension artérielle essentielle est une maladie complexe, multifactorielle et polygénique. Même si on a identifié de nombreux facteurs de risque de l’hypertension artérielle, on ne comprend pas encore clairement les mécanismes qui la régissent. Les kinases hépatocytes produisant l’érythropoïétine (Eph) constituent la plus grande famille des récepteurs tyrosine kinase qui se lient à des ligands de surface cellulaire appelés éphrines sur les cellules avoisinantes. On sait que les interactions de Eph et des éphrines sont essentielles aussi bien dans les processus de développement que dans le fonctionnement des organes et des tissus adultes. Cependant on n’a pas encore étudié la relation entre Eph/éphrines et l’hypertension artérielle. Nous avons créé des modèles de souris knockout (K.O.) Ephb6-/-, Efnb1-/- et Efnb3-/- pour cette étude. Dans le modèle EphB6-/-, nous avons observé que les souris K.O. Ephb6 castrées, mais pas les femelles, ainsi que les souris mâles non castrées présentaient une tension artérielle élevée (TA) par rapport à leurs homologues de type sauvage (TS). Ceci suggère que Ephb6 doit agir de concert avec l’hormone sexuelle mâle pour réguler la TA. Les petites artères des mâles castrés Ephb6-/- présentaient une augmentation de la contractilité, une activation de RhoA et une phosphorylation constitutive de la chaîne légère de la myosine (CLM) lorsque comparées à celles de leurs homologues TS. Ces deux derniers résultats indiquent que la phosphorylation de CLM et de RhoA passe par la voie de signalisation de Ephb6 dans les cellules du muscle lisse de la paroi vasculaire (CMLV). Nous avons démontré que la réticulation de Efnbs mais non celle de Ephb6 aboutit à une réduction de la contractilité des CMLV. Ceci montre que l’effet de Ephb6 passe par la signalisation inversée à travers Efnb. Dans le modèle Efnb1-/- conditionnel spécifique au muscle lisse, nous n’avons observé aucune différence entre Efnb1-/- et les souris de TS concernant la mesure de la TA dans des conditions normales. Cependant, la TA des souris K.O. Efnb1 lors d’un stress d’immobilisation est supérieure à celle des souris de TS. Dans les petites artères des souris K.O. Efnb1, le rétrécissement et la phosphorylation de CLM étaient élevés. In vitro, la contractilité et l’activation RhoA de la CMLV des souris TS étaient augmentées quand leur Efnb1 était réticulé. Ces résultats corroborent ceux des souris KO Ephb6 et prouvent que l’effet de Ephb6 dans le contrôle de la TA se produit au moins par l’intermédiaire d’un de ses ligands Efnb1 dans les CMLV. Dans le modèle Efnb3-/-, on a observé une augmentation de la TA et du rétrécissement des vaisseaux chez les femelles Efnb3-/-, mais non chez les mâles; l’échographie a aussi révélé une résistance accrue au débit sanguin des souris K.O. femelles. Cependant la mutation de Efnb3 ne modifie pas la phosphorylation de la CLM ou l’activation de RhoA in vivo. Dans l’expérience in vitro, les CMLV des souris femelles Efnb3-/- ont présenté une augmentation de la contractilité mais pas celle des souris mâles Efnb3-/-. La réticulation des CMLV chez les mâles ou les femelles de TS avec solide anti-Efnb3 Ab peut réduire leur contractilité. Notre étude est la première à évaluer le rôle de Eph/éphrines dans la régulation de la TA. Elle montre que les signalisations Eph/éphrines sont impliquées dans le contrôle de la TA. La signalisation inverse est principalement responsable du phénotype élevé de la TA. Bien que les Efnb1, Efnb3 appartiennent à la même famille, leur fonction et leur efficacité dans la régulation de la TA pourraient être différentes. La découverte de Eph/Efnb nous permet d’explorer plus avant les mécanismes qui gouvernent la TA.