Background: The urinary bladder requires a rich blood supply to maintain its functions, the storage and release of urine. Specialized properties of the bladder vasculature might be anticipated to ensure the integrity of this blood supply, because it is known that blood flow is reduced by distension during bladder filling. However, the bladder vasculature has been described in detail only at the gross level. A comprehensive, threedimensional view of the blood supply to the bladder wall is presented here. Methods: The microvasculature of the bladder of male New Zealand white rabbits was described using the combination of vascular corrosion casting, alkali digestion, light microscopy, and scanning and transmission electron microscopy. Following administration of an anticoagulant and an overdose of anesthetic, the abdominal aorta was cannulated just above the inferior mesenteric artery to permit flushing of the distal vasculature. The bladder vasculature was cleared of blood with buffered saline and then either perfuse‐fixed with buffered 2% glutaraldehyde and sectioned, or filled with “Mercox” resin to prepare vascular corrosion casts. Casts were cleaned with NaOH, formic acid, and water. In some cases fixed bladders were partially digested with NaOH to expose the mucosal capillary plexus. Results: The bladder is supplied with blood by single, left and right vesicular branches of the internal or external iliac arteries. The serpentine vesicular arteries extend along the lateral borders of the bladder from base to apex just deep to the serosal surface and send dorsal and ventral branches to supply the dorsal and ventral bladder walls. Veins accompany the arteries and exhibit numerous valves. A very dense complex of vessels at the apex of the bladder apparently serves to accommodate bladder distension. The muscularis and submucosa contains few vessels, but the mucosa is well vascularized. An especially dense capillary plexus is present in the lamina propria at its junction with the transitional epithelium. In the relaxed bladder these capillaries lie in grooves formed by the basal layers of the epithelium. The endothelial cells of these capillaries display few cytoplasmic vesicles and are continuous or fenestrated. These capillaries are often invested with pericytes. The mucosal capillary plexus may be associated with an epithelial transport function or may be necessary for urothelial metabolism or maintenance of the barrier function of the urothelium. Unusual capillary tufts, possibly associated with vascular lymphatic tissue, are found associated with the main vessels on the lateral walls in the basal half of the bladder. Conclusions: These methods present a clear, comprehensive, three‐dimensional view of the microvasculature of the bladder wall. They also identify several unique features of this vasculature and provide a basis for studies of the response of this vasculature to pathologic states and experimental manipulation.

Asphaltenic crude oil is a complex fluid containing various components with different chemical properties. When it comes in contact with water, its polar components adsorb at the oil/water interface, reducing the interfacial tension and eventually developing viscoelastic films. The interfacial films impact emulsion stability and adhere to the oil-bearing reservoirs rocks, altering their wettability and thus hindering oil mobilization. Here, we investigate the formation of crude oil/water interfacial films. We measure both the time-dependent shear and extensional interfacial rheology moduli, and we relate it to the chemical composition of the films, highlighting the role of polar aromatic molecules in film formation. Varying chemical composition of the aqueous phase, we show that the properties of the interfacial films depend not only on the concentration of ionic species in water but also on their chemical nature. In particular, we highlight the role of sulfate salt in promoting interfacial viscoelasticity and in altering the composition of fully developed films. To study the rock/fluid interaction, we fabricate mixed-wet capillaries with angular cross-sections inspired by the naturally occurring primary drainage of pore-filling brine by invading crude oil. After employing our novel coating procedure, we experimentally investigate water invasion in mixed-wet capillaries and compare it with predictions of dynamic and quasi-static (Mayer-Stowe-Princen (MSP)) meniscus-invasion models. None of the dynamic models built for uniformly-wet pores can fully describe our experimental data in mixed-wet capillaries. However, the experimental results agree with predictions of MSP theory. To our knowledge, this is the first direct experimental validation of MSP theory under mixed-wet conditions. We confirm the possibility of spontaneous piston-type imbibition with high ($> 90^{\circ}$) advancing contact angles into mixed-wet pores, given that the contact angle is lowered below a critical value that is a function of pore geometry and residual water saturation. In oil reservoirs, injection of specific brines would be required to change the contact angle to values below the imbibition threshold. Finally, we extend our study and introduce a powerful 3D high-speed laser imaging of dynamic fluid flow in angular capillaries and investigate its capability to capture non-equilibrium shapes of fluid interfaces.

Skeletal muscle possesses a remarkable plasticity, able to repair, remodel and adapt to various stressors. A population of resident muscle stem cells, commonly referred to as satellite cells (SC), are largely responsible for skeletal muscle plasticity. The loss of muscle mass and plasticity typically observed in aging has been attributed to the deterioration of SC function. SC reside in a quiescent state, but following stimuli they become active, proliferate and eventually differentiate, fusing to existing muscle fibres. The progression of SC through this process, termed the myogenic program, is orchestrated by a complex network of transcription factors, termed myogenic regulatory factors. SC function is regulated by various growth factors and/or cytokines. The delivery of these signalling factors to SC is, in part, dependent on their proximity and exposure to local microvascular blood flow. The purpose of this thesis was to examine the relationship between skeletal muscle capillaries and muscle SC. We examined the effect of age on the spatial relationship between SC and muscle fiber capillaries, and observed that type II muscle fiber SC were located at a greater distance from the nearest capillary in older men as compared to their younger counterparts. We then examined the changes in SC activation status following a single bout of resistance exercise, prior to and following a 16wk progressive resistance training (RT) program. We observed that following RT, there was an enhanced SC activation in response to a single bout of resistance exercise. This enhanced response was accompanied by an increase in muscle capillarization following training. Furthermore, we investigated the impact of muscle fiber capillarization on the expansion and activation status of SC in acute response to muscle damaging exercise in healthy young men. We observed that muscle capillarization was positively related to SC pool activation and expansion. Taken together, we demonstrate that muscle capillarization may be related to the SC response following acute resistance exercise or exercise-induced injury, and may be implicated in adaptation to RT. Furthermore, the spatial relationship between muscle capillaries and SC is negatively altered by aging. / Thesis / Doctor of Philosophy (PhD) / Skeletal muscle health is, in part, maintained by a population of stem cells associated with individual muscle fibres. When muscle is damaged or stressed, these cells become activated, aid in muscle repair, and help drive adaptations to exercise. The central purpose of this thesis was to examine the relationship between muscle capillaries and muscle stem cells, and determine how that relationship impacts muscle stem cell function. We demonstrated that muscle stem cells and capillaries exist in close proximity to each other in skeletal muscle. We observed that a greater muscle capillarization is linked to improved muscle stem cell function during muscle repair. However, we also report that the distance between muscle capillaries and muscle stem cells becomes greater in aging, and may be a root cause of impaired muscle stem cell function in aging.

[pt] O escoamento de emulsões é encontrado em diversos processos de recuperação e produção de petróleo. O escoamento de emulsões em meios porosos depende de diversos parâmetros como a relação do tamanho das gotas ao tamanho dos poros, a razão de viscosidades, a vazão volumétrica e o efeito destes parâmetros ainda não é bem compreendido. Uma análise detalhada na escala microscópica dos fenômenos envolvidos se faz essencial para a melhora do entendimento completo do escoamento de emulsões em um reservatório. Isto permitiria o desenvolvimento de melhores modelos de simulação para o escoamento multifísico em meios porosos. Neste trabalho, o escoamento de emulsões óleo-água através de um capilar com garganta foi estudado através de experimentos e teoria. A análise experimental consistiu da visualização sob um microscópio do escoamento e da medição da queda de pressão em função da vazão para diferentes emulsões. A análise teórica englobou o estudo do escoamento em regime permanente de uma gota de óleo imersa em água através de um capilar e o estudo do escoamento transiente da mesma gota através de um capilar com uma garganta. Os resultados mostram que os modelos de escoamento de emulsões em meios porosos não devem ser baseados em propriedades macroscópicas da emulsão quando o tamanho das gotas da fase dispersa for da mesma ordem de grandeza do tamanho dos poros. Neste caso, a queda de pressão é função da tensão interfacial, a razão de viscosidades, a vazão e a razão entre o tamanho das gotas e o diâmetro do poro. Os resultados apresentados neste trabalho podem ser usados no projeto de emulsões apropriadas para controle de mobilidade em operações de recuperação avançada através de injeção de emulsões. / [en] Flow of emulsions is found in many petroleum recovery and production processes and it is often referred to in the context of tertiary oil recovery. The characteristics of emulsion flow in porous media depend on several parameters such as medium drop size to pore size ratio, viscosity ratio, flow rate and the effect of these parameters is far from being entirely understood. A detailed analysis at a microscopic scale of the flow is essential to improve the understanding of flow of an emulsion in a reservoir. This would lead to the development of better simulation models, henceforth increasing the predictability capability of reservoir simulators for enhanced oil recovery applications. In this work, flow of oil-water emulsions through constricted capillaries, used as model for the geometry inside a porous media, is studied experimentally and theoretically. The experimental approach consisted of measuring pressure drop response as a function of flow rate for different emulsions and visualizing the flow under an optical microscope to understand the phenomena involved. The theoretical approach is divided in two parts. First, the immiscible steady flow of a infinite single drop suspended in an less viscous fluid through a capillary was analyzed by solving the Navier- Stokes equations with the appropriate boundary conditions for free-surface flow. The second part of the theoretical analysis consisted of solving the transient flow of a drop suspended in a less viscous fluid through a capillary with a constriction. It is shown the effect of capillary number and viscosity ratio over the main responses of the flow. The results show that models of emulsion flow in a porous media cannot be based on the macroscopic properties of the emulsion when the drop diameter is of the same order of magnitude as the pore throat diameter. In this case flow rate-pressure drop is a strong function of the interfacial tension, viscosity ratio, flow rate and drop to pore size ratio. The results can be used to design appropriate emulsions to control the water mobility during EOR operations by emulsion injection.

L’imagerie fonctionnelle cérébrale détecte les changements hémodynamiques induits par un stimulus pour déterminer les zones d’activation neuronale. Plus particulièrement, l’imagerie BOLD en IRMf détecte les changements d’oxygénation du sang grâce aux propriétés paramagnétiques de la déoxyhémoglobine. L’oxygène n’est donc pas uniquement un substrat énergétique pour le tissu neuronal, il joue également un rôle majeur dans l’imagerie noninvasive du cerveau humain. Au cours de ma thèse, j’ai tout d’abord participé à la mise au point d’une nouvelle technique non-invasive d’imagerie de l’oxygène dans le cerveau d’animaux anesthésiés. Couplant un nouveau senseur phosphorescent de l’oxygène (Finikova et al., 2008) et la microscopie biphotonique, cette approche permet à la fois de cartographier l’oxygène en 3D avec une résolution spatiale et temporelle jusqu’alors inégalée, mais aussi de suivre simultanément l’oxygène et le flux sanguin dans les capillaires cérébraux au repos ou lors d’une activation neuronale (Lecoq et al., 2011). Tirant profit des nouvelles possibilités de cette technique, nous avons alors démontré: • la présence d’un shunt artério-veineux uniquement basé sur la diffusion de l’oxygène. Ce résultat, obtenu chez le rat dans la couche la plus superficielle du bulbe olfactif: la couche du nerf (ONL), confirme que l’oxygène ne diffuse pas uniquement à partir des capillaires et démontre que les artérioles contribuent significativement à l’oxygénation du tissu cérébral. Il démontre également qu’il n’est pas possible de déterminer ni la Po2 capillaire ni la Po2 tissulaire à partir de la Po2 veineuse. • l’existence de transitoires de Po2 associés à chaque globule rouge dans le compartiment capillaire, appelés EATs (erythrocyte-associated transients) (Hellums, 1977; Cabrales and Intaglietta, 2007). En bref, de part leur diamètre supérieur à celui de la lumière d’un capillaire, les globules rouges passent un à un dans la lumière des capillaires, laissant entre eux un espace de plasma. Cependant, la faible solubilité de l’oxygène dans le plasma crée une barrière à la diffusion, ce qui se traduit par une inhomogénéité de la Po2 capillaire: celle-ci est élevée au bord du globule rouge et décroit avec la distance pour atteindre un minimum à mi-distance entre deux globule rouges. Poursuivant l’étude des EATs (Parpaleix et al., 2013), nous avons observé les points suivants: • La Po2 tissulaire dans l’environnement immédiat d’un capillaire peut être déterminée à partir de la Po2 vasculaire à mi-distance entre deux érythrocytes. Ce résultat est intéressant en ce qu’il permettra d’effectuer des mesures non invasives de Po2 tissulaire, utile notamment chez l’animal éveillé. • L’amplitude des EATs est si large (35 mmHg en moyenne) que la Po2 capillaire moyenne ne reflète en rien la saturation en oxygène de l’hémoglobine. • Une empreinte filtrée des EATs vasculaires est détectable dans le tissu (_5 mmHg d’amplitude). • Au cours d’une stimulation neuronale, une diminution de la Po2 capillaire moyenne peut être détectée avant l’hyperémie fonctionnelle, un résultat jusqu’à présent controversé dans le domaine de l’imagerie BOLD en IRMf, mais important en ce que ce dip pourrait être un rapporteur très résolutif de l’activation neuronale. Parmi les questions restant en suspens et pouvant être étudiées finement avec notre approche, j’en citerai une principale: quel est le poids des différents facteurs (métaboliques, présynaptiques ou post-synaptiques) et du flux sanguin dans l’établissement de la Po2 cérébrale au repos? / In humans, functional mapping of brain activity mainly relies on the increase of cerebral blood flow (CBF) triggered by neuronal activation. This neurovascular coupling provides energy substrates such as oxygen and glucose to the activated area. The steady state concentration of oxygen, as well as its dynamics upon neuronal activation, have been investigated with numerous methods, however, none of them provided highly resolute measurements in depth. During my PhD, we combined a phosphorescence quenching approach with two-photon microscopy to detect, in depth and with a micrometer spatial resolution scale, the emission of phosphorescence by PtP-C343, a new oxygen nano-sensor designed for two-photon excitation. We first characterized the technique and then reported two biological results, using the olfactory bulb (OB) glomerulus as a model to study oxygen concentration, at rest and upon odor stimulation. We found an arterio-venous shunt, purely based on diffusion, in the superficial nerve layer of the OB, confirming the role of arterioles in brain oxygenation. Simultaneous measurements of Po2 and blood flow allowed us to reveal the presence of erythrocyte-associated transients (EATs), i.e. Po2 fluctuations that are associated with individual erythrocytes. Pursuing the investigation of EAT characteristics, we found that in capillaries, Po2 at mid-distance between two erythrocytes is at equilibrium with, and thus reports Po2 in the nearby neuropil. Finally, we could observe that even in capillaries, a small oxygen initial dip can be detected prior to functional hyperemia, upon odor activation.

La consommation mondiale d'énergie a fortement augmenté durant le siècle dernier et va continuer de croître au cours des prochaines décennies. Le développement d'énergies durables et alternatives aux énergies fossiles constitue un enjeu crucial pour les générations futures. Dans ce contexte, la fusion thermonucléaire contrôlée serait un candidat de premier choix pour assurer la transition énergétique. Le tokamak, basé sur la fusion par confinement magnétique, est actuellement la solution la plus en vue pour contrôler la réaction de fusion et utiliser cette énergie à des fins civiles.Dans les plasmas de tokamak, les impuretés lourdes comme le tungstène présent dans les éléments de la paroi face au plasma, peuvent migrer vers le plasma de cœur et fortement dégrader les performances fusion par rayonnement. L’objectif de cette thèse est d’utiliser ce rayonnement dans la gamme des X-mous afin d’en déduire des informations sur le transport du tungstène dans le plasma de cœur. Le but est de contrôler à terme cette concentration en impuretés et d’identifier les actuateurs pouvant agir sur cette distribution. / Global energy consumption has increased significantly during the last century and will continue to grow in the coming decades. The development of sustainable energies alternative to fossil fuels is a crucial issue for the future generations. In this context, controlled thermonuclear fusion is a good candidate for the energy transition. Magnetic confinement fusion and tokamaks are currently the most promising solution to control the fusion reaction and use it for civil purposes.In tokamak plasmas, heavy impurities such as tungsten sputtered from plasma-facing components can migrate to the core plasma and strongly degrade fusion performance by radiation. The goal of this PhD thesis is to use this radiation in the soft X-ray range in order to obtain valuable information on tungsten transport in the core plasma. The final perspective is to control the impurity concentration and identify actuators that can act on this distribution.

Raman spectroscopy, laser-induced fluorescence, and sum-frequency generation (SFG) spectroscopy are used to investigate the behavior of compressible mobile phases and stationary phases under a variety of chromatographic conditions. Efforts to understand and optimize separations employing compressible mobile phases have been limited by a lack of understanding of the mobile phase density gradient. Mobile phase compressibility leads to gradients in linear velocity and solute retention and affects separation speed and efficiency, especially in packed columns. This work describes on-column density measurement of CO2, a common carrier fluid for SFC and SGC, in packed capillary columns using Raman microspectroscopy. On-column detection by laser-induced fluorescence is used to observe the effect of the mobile phase density gradient on separation speed and efficiency, and experimental efficiency is compared to a theoretical model. Additionally, SFG spectroscopy allows for probing the structure of model monomeric and polymeric C18 stationary phases under pressure; this provides a basis for correlating selectivity with pressure-induced structural changes in stationary phase materials. Together, this work provides a more complete understanding of the role of column pressure and fluid compressibility on the speed, efficiency, and selectivity of chemical separations.

Les cellules murales du cerveau sont un groupe de cellules neurovasculaires qui présentent une hétérogénéité moléculaire, morphologique et fonctionnelle exceptionnelle. Celles en contact avec les plus petis vaisseaux du cerveau, les péricytes du lit capillaire moyen sont connues pour être essentielles à l'homéostasie cérébrale, bien que leur capacité contractile ait longtemps été débattue. Cependant, nombre de leurs propriétés physiologiques, telles que leurs mécanismes de signalisation calcique, n'ont pas encore été élucidées. Cette thèse vise donc à identifier les mécanismes cellulaires de la signalisation calcique des péricytes des capillaires cérébraux. Dans le chapitre 2, nous utilisons la pharmacologie et l'imagerie des péricytes cérébraux exprimant l'indicateur de calcium GCaMP6f (provenant de souris transgéniques PDGFRβ-Cre::GCaMP6f) pour découvrir ces mécanismes. Contrairement aux péricytes engainants dont la signalisation du calcique dépend des canaux calcique voltage-dépendants, nous constatons que les signaux calcique des péricytes capillaire moyen sont indépendants des canaux calcique voltage-dépendants. Au contraire, nous constatons que les signaux calciques transitoires des pericytes du lit capillaire moyen sont inhibés par l'élimination du Ca2+ extracellulaire, l'inhibition des canaux Orai opérés par les réserves, le blocage du remplissage des réserves du réticulum endoplasmique, ainsi que l'inhibition des récepteurs de la ryanodine (RyRs) et des récepteurs de l'inositol trisphosphate (IP3Rs). Nous constatons également que l'entrée de Ca2+ opérée par les réserves peut être induite par la déplétion des réserves du réticulum endoplasmique et inhibée par les bloqueurs d'Orai dans les pericytes du lit capillaire moyen, et que l'influx basal de Ca2+ est largement dépendant de la déplétion des réserves. Enfin, nous montrons que l'entrée de Ca2+ opérée par les réserves d'Orai amplifie les élévations de Ca2+ cytosolique en réponse au vasoconstricteur endothéline-1. Nous concluons que la signalisation calcique dans les pericytes du lit capillaire moyen, qu'elle soit spontanée ou induite de façon agoniste, est régulée par le couplage entre la libération des réserves du réticulum endoplasmique et les voies d'influx opérées par les réserves. / Brain mural cells are a grouping of neurovascular cells that display exceptional molecular, morphological, and functional heterogeneity. Mid-capillary pericytes, the mural cells which contact the smallest vessels of the brain, are known to be critical to brain homeostasis, and their contractile ability has long been debated. However, many of their physiological properties, such as their Ca2+ signaling mechanisms, have not been elucidated. This thesis aims to uncover the cellular mechanisms of brain mid-capillary pericyte Ca2+ signaling. In chapter 2, we harness pharmacology and imaging of brain pericytes expressing the calcium indicator GCaMP6f (from transgenic PDGFRβ-Cre::GCaMP6f mice) to uncover these mechanisms. In contrast to ensheathing pericytes whose Ca2+ signaling is dependent on voltage-gated Ca2+ channels (VGCCs), we find that mid-capillary pericyte Ca2+ signals are independent of VGCCs. Instead, we find that mid-capillary pericyte Ca2+ transients are inhibited by removal of extracellular Ca2+, inhibition of store-operated Orai channels, blockade of endoplasmic reticulum store filling, as well as inhibition of ryanodine receptors (RyRs) and inositol triphosphate receptors (IP3Rs). We further find that store-operated Ca2+ entry can be induced by endoplasmic reticulum store depletion and inhibited by Orai blockers in mid-capillary pericytes, and that basal Ca2+ influx is largely dependent on store depletion. Finally, we show that Orai store-operated Ca2+ entry amplifies cytosolic Ca2+ elevations in response to the vasoconstrictor endothelin-1. We conclude that both spontaneous and Gq-coupled protein receptor agonist-induced Ca2+ signaling in mid-capillary pericytes is regulated by coupling between endoplasmic reticulum store release and store-operated influx pathways.

Purpose: To review the roles of the different vascular beds nourishing the inner retina [retinal ganglion cells (RGCs)] during normal development of the human eye, using our own tissue specimens to support our conclusions. Methods: An extensive search of the appropriate literature included PubMed, Google scholar, and numerous available textbooks. In addition, choroidal and retinal NADPH-diaphorase stained whole mount preparations were investigated. Results: The first critical interaction between vascular bed and RGC formation occurs in the sixth to eighth month of gestation leading to a massive reduction of RGCs mainly in the peripheral retina. The first 3 years of age are characterized by an intense growth of the eyeball to near adult size. In the adult eye, the influence of the choroid on inner retinal nutrition was determined by examining the peripheral retinal watershed zones in more detail. Conclusion: This delicately balanced situation of RGC nutrition is described in the different regions of the eye, and a new graphic presentation is introduced to combine morphological measurements and clinical visual field data.

Estudos demonstram que o treinamento aeróbio é capaz de reduzir a razão parede/luz (RP/L) de arteríolas musculares esqueléticas e reduzir a pressão arterial média, PAM (em hipertensos), além de causar bradicardia de repouso e aumentar a densidade de capilares e vênulas (em hipertensos e normotensos) após 13 semanas de treinamento. Investigamos em ratos normotensos (WKY, Wistar Kyoto) e hipertensos espontâneos (SHR) as alterações estruturais da microcirculação muscular esquelética, cardíaca e renal, relacionando-as aos valores de PAM e frequência cardíaca (FC) em diferentes fases de um protocolo de treinamento. Para tal, WKY e SHR (2 meses de idade) foram submetidos ao protocolo de treinamento físico de baixa intensidade por tempos crescentes (semanas 0, 1, 2, 4, 8 e 12) ou mantiveram-se sedentários (semanas 0 e 12). Ao final de cada tempo de estudo foram mensurados de modo direto a PAM e a FC e coletados coração, rim e músculos temporal, sóleo e gastrocnêmio. Realizou-se análise da RP/L e quantificação de capilares e vênulas (através do ácido periódico de Schiff). O treinamento aeróbio aumentou a densidade capilar e venular de WKY e SHR (apenas em territórios exercitados e com maior magnitude nos hipertensos), em seguida causou redução da razão parede/luz das arteríolas musculares esqueléticas (apenas em SHR, precocemente e em maior magnitude em territórios exercitados) e só então reduziu a PAM de SHR e a FC de WKY e SHR. A partir dos resultados obtidos, podemos dizer que alterações estruturais da microcirculação antecedem a melhora dos níveis pressóricos de hipertensos e ainda, são capazes de proporcionar melhoras vasculares aos normotensos / Previous observations have shown that aerobic training reduce the wall/lumen ratio (RW/L) of skeletal muscle arterioles and reduce mean arterial pressure (MAP) in hypertensive rats, cause bradycardia, and increase capillary and venular density also in hypertensive and normotensive rats after 13 weeks of training. We investigated simultaneously the time-course changes of arterioles remodeling, MAP, HR and capillary and venular density during the development of low-intensity exercise protocol. Normotensive rats (WKY, Wistar Kyoto) and spontaneously hypertensive (SHR), two-months old were submitted to aerobic training protocol (weeks 0, 1, 2, 4, 8 and 12) or remained sedentary (weeks 0 and 12). In each study time were measured the MAP and HR and collected heart, kidney, temporalis, soleus and gastrocnemius muscles to analyze the RW/L and quantificate capillaries and venules (by Periodic Acid-Schiff staining). Aerobic training increased capillary and venular density of WKY and SHR (only in exercised territories), caused a reduction of the RW/L of skeletal muscle arterioles (only in SHR, early and in greater magnitude in exercised territories) and only then reduced MAP of SHR and HR of WKY and SHR. The structural changes of microcirculation preceded improvement of blood pressure levels in hypertensive rats and provided vascular improvements to normotensive rats