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<p>The gastric mucosa is frequently exposed to endogenously secreted hydrochloric acid of high acidity. Gastric mucosal defense mechanisms are arranged at different levels of the gastric mucosa and must work in unison to maintain its integrity. </p><p>In this thesis, several mechanisms underlying gastric mucosal resistance to strong acid were investigated in anesthetized rats and mice. The main findings were as follows:</p><p>Only when acid secretion occurred did the pH gradient in the mucus gel withstand back-diffusion of luminal acid (100 mM or 155 mM HCl), and keep the juxtamucosal pH (pH_jm) neutral. Thus, when no acid secretion occurred and the luminal pH was 0.8-1, the pH gradient was destroyed. </p><p>Bicarbonate ions, produced concomitant with hydrogen ions in the parietal cells during acid secretion and blood-borne to the surface epithelium, were carried transepithelially through a DIDS-sensitive transport. </p><p>Prostaglandin-dependent bicarbonate secretion seemed to be less important in maintaining a neutral pH_jm. </p><p>Removal of the loosely adherent mucus layer did not influence the maintenance of the pH_jm. Hence, only the firmly adherent mucus gel layer, approximately 80µm thick, seemed to be important for the pH_jm. </p><p>Staining of the mucus gel with a pH-sensitive dye revealed that secreted acid penetrated the mucus gel from the crypt openings toward the gastric lumen only in restricted paths (channels). One crypt opening was attached to one channel, and the channel was irreversibly formed during acid secretion. </p><p>Gastric mucosal blood flow increased on application of strong luminal acid (155 mM HCl). This acid-induced hyperemia involved the inducible but not the neural isoform of nitric oxide synthase. These results suggest a novel role for iNOS in gastric mucosal protection and indicate that iNOS is constitutively expressed in the gastric mucosa. </p><p>It is concluded that a pH gradient in the gastric mucus gel can be maintained during ongoing acid secretion, since the acid penetrates the mucus only in restricted channels and bicarbonate is carried from the blood to the lumen via a DIDS-sensitive transporter.</p>

The gastric mucosa is frequently exposed to endogenously secreted hydrochloric acid of high acidity. Gastric mucosal defense mechanisms are arranged at different levels of the gastric mucosa and must work in unison to maintain its integrity. In this thesis, several mechanisms underlying gastric mucosal resistance to strong acid were investigated in anesthetized rats and mice. The main findings were as follows: Only when acid secretion occurred did the pH gradient in the mucus gel withstand back-diffusion of luminal acid (100 mM or 155 mM HCl), and keep the juxtamucosal pH (pHjm) neutral. Thus, when no acid secretion occurred and the luminal pH was 0.8-1, the pH gradient was destroyed. Bicarbonate ions, produced concomitant with hydrogen ions in the parietal cells during acid secretion and blood-borne to the surface epithelium, were carried transepithelially through a DIDS-sensitive transport. Prostaglandin-dependent bicarbonate secretion seemed to be less important in maintaining a neutral pHjm. Removal of the loosely adherent mucus layer did not influence the maintenance of the pHjm. Hence, only the firmly adherent mucus gel layer, approximately 80µm thick, seemed to be important for the pHjm. Staining of the mucus gel with a pH-sensitive dye revealed that secreted acid penetrated the mucus gel from the crypt openings toward the gastric lumen only in restricted paths (channels). One crypt opening was attached to one channel, and the channel was irreversibly formed during acid secretion. Gastric mucosal blood flow increased on application of strong luminal acid (155 mM HCl). This acid-induced hyperemia involved the inducible but not the neural isoform of nitric oxide synthase. These results suggest a novel role for iNOS in gastric mucosal protection and indicate that iNOS is constitutively expressed in the gastric mucosa. It is concluded that a pH gradient in the gastric mucus gel can be maintained during ongoing acid secretion, since the acid penetrates the mucus only in restricted channels and bicarbonate is carried from the blood to the lumen via a DIDS-sensitive transporter.

The overall aim of this thesis was to combine optical methods into a system with the ability to simultaneously measure blood flow changes at different tissue depths. The goal of such a system was to reveal vascular mechanisms relevant to pressure ulcer etiology under clinically relevant conditions and in relation to the evaluation of pressure-redistribution support surfaces. This thesis consists of four quantitative, cross-sectional studies measuring blood flow responses before, during, and after pressure exposure of the sacral tissue. Two optical methods – photoplethysmography and laser Doppler flowmetry – were combined in a newly developed system that has the ability to discriminate blood flows at different tissue depths. Studies I and II explored blood flow responses at different depths in 17 individuals. In Study I the blood flow was related to tissue thickness and tissue compression during pressure exposure of ≥ 220 mmHg. In Study II, the sacral tissue was loaded with 37.5 mmHg and 50.0 mmHg, and the variation in blood flow was measured. Studies III and IV included 42 healthy individuals &lt; 65 years, 38 healthy individuals ≥ 65 years, and 35 patients ≥ 65 years. Study III included between-subject comparisons of blood flow and pressure between individuals in the three study groups lying in supine positions on a standard hospital mattress. Study IV added within-subject comparisons while the individual was lying on four different types of mattress. The studies explored the vascular phenomena pressure-induced vasodilation (PIV) and reactive hyperemia (RH). The most common blood flow response to tissue exposure in this thesis was PIV, although a decrease in blood flow (a lack of PIV) was observed in some individuals. The patients tended to have higher interface pressure during pressure exposure than the healthy groups but no differences in blood flow responses were seen. Our results showed that pressure levels that are normally considered to be harmless could have a significant effect on the microcirculation in different tissue structures. Differences in individual blood flow responses in terms of PIV and RH were seen, and a larger proportion of individuals lacked these responses in the deeper tissue structures compared to more superficial tissue structures. This thesis identified PIV and RH that are important vascular mechanisms for pressure ulcer development and revealed for the first time that PIV and RH are present at different depths under clinically relevant conditions. The thesis also identified a population of individuals not previously identified who lack both PIV and RH and seem to be particularly vulnerable to pressure exposure. Further, this thesis has added a new perspective to the microcirculation in pressure ulcer etiology in terms of blood flow regulation and endothelial function that are anchored in clinically relevant studies. Finally, the evaluation of pressureredistribution support surfaces in terms of mean blood flow during and after tissue exposure was shown to be unfeasible, but the assessment of PIV and RH could provide a new possibility for measuring individual physiological responses that are known to be related to pressure ulcer development.

Thesis (M.Eng. (Hons.)) -- University of Western Sydney, 2001. / Bibliography : leaves [185]-195 (v. 1).

Submitted by Mario BC (mario@bc.ufrpe.br) on 2016-06-13T13:47:43Z No. of bitstreams: 1 Maria Albeline Silva de Lacerda.pdf: 765473 bytes, checksum: c89c99400df21609a6c505748d7ff4d1 (MD5) / Made available in DSpace on 2016-06-13T13:47:43Z (GMT). No. of bitstreams: 1 Maria Albeline Silva de Lacerda.pdf: 765473 bytes, checksum: c89c99400df21609a6c505748d7ff4d1 (MD5) Previous issue date: 2015-02-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The hemodynamic of uterine arteries and the adequate blood supply are important to the uterine physiology. The aim of this study was to determine patterns of flowmetry of uterine arteries using Doppler ultrasonography, in physiologic conditions (estrous cycle) and pathologic (pyometra). The animals (n=56) were distributed in heterogenic samples of each phase of estrous cycle (proestrous – n=7, estrous – n=5, dietrous – n= 19 and anestrous – n=13) or pyometra (n=12). All studied animals were submitted to ultrasound mode B exam, and media uterine artery was identified using Doppler tools. The pulsativity (IP), resistivity (IR) and systole/diastole (S/D) indexes and diastolic end (ED), systolic pick (PS), TAMAX, and heart rhythm (HR) were automatically determined by the ultrasound machine. The results showed that there is no significant difference between analyzed parameters and estrous cycle phases. However, comparing healthy animals in diestrus with pyometra, higher averages (P <0.05) of IP (8.54 ± 5.92) and IR (1.00 ± 0.11) was observed in the healthy compared to those with pyometra (PI = 4.49 ± 2.51 and 0.89 ± IR = 0.13). It was also observed higher mean TAMAX in pyometra (6.09 ± 15.09 cm/s) compared to healthy animals (2.72 ± 1.94 cm/s). With respect to the PS, a tendency (P = 0.07) of higher mean value was observed in pyometra (29.8 ± 15.35 cm/s) compared to healthy animals in diestrus phase (23.08 ± 8.61 cm/s). The other parameters showed no difference between groups. It was concluded that the phases of the estrous cycle do not interfere with hemodynamic parameters. Furthermore, the uterine artery blood flow has increased speed and decreased vascular resistance associated with pyometra. / A hemodinâmica das artérias uterinas e o adequado suprimento sanguíneo são importantes para a fisiologia úterina. Assim, objetivou-se estabelecer relações da condição fisiológica (em diferentes fases do ciclo estral) e patológica (piometra) com os parâmetros hemodinâmicos obtidos pela ultrassonografia Doppler colorido e pulsado, em artérias uterinas médias de cadelas. Foram utilizadas 56 cadelas, divididas em fases do ciclo estral: proestro (n=7), estro (n=5), diestro (n=19) e anestro (n=13); e piometra (n=12). Para o exame ultrassonográfico foi utilizado equipamento portátil (M5, Mindray), com sonda convexa (4–8 MHz), para medir automaticamente os índices de pulsatilidade (IP), resistividade (IR), relação sístole/diástole (S/D), velocidades final diastólica (ED), do pico sistólico (PS) e Velocidade Máxima Média do Ciclo (TAMAX), além da frequência cardíaca (HR). O útero foi identificado na avaliação modo-B e, em seguida acionado o modo Doppler, com ângulo de insonação ≤60º. Os resultados fluxométricos não mostraram diferenças entre as fases do ciclo estral. Porém, quando comparados animais em diestro saudável com os apresentando piometra, maiores médias (P<0,05) de IP (8,54±5,92) e IR (1,00±0,11) ocorreram nos saudáveis comparados aos com piometra (IP = 4,49±2,51 e IR = 0,89±0,13). Também foi observada maior média de TAMAX nos com piometra (6,09±15,09 cm/s) comparada aos saudáveis (2,72±1,94 cm/s). Com relação ao PS, foi observada uma tendência (P=0,07) de maior média nos com piometra (29,8±15,35 cm/s) comparados aos saudáveis na fase de diestro (23,08±8,61 cm/s). Os outros parâmetros não mostraram diferença entre os grupos. Conclui-se que as fases do ciclo estral não interferem nos parâmetros hemodinâmicos estudados. Por outro lado, a artéria uterina média apresenta aumento da velocidade de fluxo sanguíneo e diminuição da resistência vascular associada à piometra.

<p>The human stomach normally contains high levels of bioactive nitric oxide (NO). This NO derives from salivary nitrate (NO₃^-) that is converted to nitrite (NO₂^-) by oral bacteria and thereafter non-enzymatically reduced in the acidic gastric lumen to NO. Nitrate is a common component in vegetables, and after ingestion it is absorbed in the small intestine. Interestingly, circulating nitrate is then concentrated by the salivary glands. Hence, intake of nitrate-rich vegetables results in high levels of NO in the stomach. The physiological effects of the high concentration of NO gas normally present in the gastric lumen have been hitherto unknown, and the present investigations were therefore conducted to address this issue.</p><p>NO produced in the gastric lumen after nitrate ingestion increased gastric mucosal blood flow and the thickness of the firmly adherent mucus layer in the stomach. The blood flow and mucus layer are essential defense mechanisms that protect the mucosa from luminal acid and noxious agents. Nonsteroidal antiinflammatory drugs (NSAID) are commonly prescribed and effective drugs for treating pain and inflammation, but are associated with severe gastrointestinal side effects. We demonstrated that a nitrate-rich diet protects against NSAID-induced gastric damage, as a result of the increased formation of NO in the stomach. We also showed that the gastroprotective effect attributed to nitrate depended completely on conversion of nitrate to nitrite by the bacterial flora colonizing the tongue, and that the oral microflora is therefore important in regulating physiological conditions in the stomach.</p><p>In summary, this thesis challenges the current dogma that nitrate intake is hazardous, and on the contrary suggests that dietary nitrate plays a direct role in regulating gastric homeostasis. It is likely that a sufficient supply of nitrate in the diet together with the oral microflora is essential for preventing pathological conditions in the gastrointestinal tract.</p>

Queimaduras severas causam trauma às vítimas, pela perda de líquido corpóreo, injúria no sistema vascular cutâneo e demora na cicatrização das lesões. A irradiação com laser em baixa intensidade vem sendo estudada como tratamento alternativo, por ser uma terapia não-invasiva e capaz de acelerar o processo de cicatrização. O objetivo deste estudo foi avaliar os efeitos do laser de baixa potência (&lambda; = 660 nm) em queimaduras de pele por histomorfometria e fluxometria laser Doppler utilizando duas condições de irradiação. Trinta e seis animais com duas queimaduras criadas por vapor foram divididos em três grupos: no grupo dose fracionada (GF), as lesões foram irradiadas com dose de 1 J/cm2 nos dias 1, 3, 8 e 10; no grupo dose única (GU), as lesões foram irradiadas com dose de 4 J/cm2 no dia 1. O grupo controle (GC) não foi irradiado. O fluxo sanguíneo foi monitorado nos dias 3, 8, 10, 15 e 21 e três animais por grupo foram sacrificados nestes momentos. Os grupos irradiados mostraram um pico de vasos neoformados no dia 15, enquanto que o pico do GC foi no dia 21. O número de vasos no GC foi significantemente maior que GF e GU no dia 21. Com relação ao fluxo sangüíneo, os grupos irradiados mostraram um valor mais alto que o controle no dia 8, porém, sem diferenças significantes entre os grupos. Estes achados sugerem que o laser acelera a cicatrização de queimaduras, porém, sem diferenças significativas entre as doses estudadas. / Severe burn injuries cause extensive damage and are notoriously complicated by loss of body fluids, injury in the cutaneous vasculature and delayed wound healing. Low intensity laser therapy (LILT) has been studied as an alternative method since it is a non invasive treatment and is able to accelerate wound healing. The purpose of the present study was to evaluate the effects of LILT (&lambda; = 660 nm) in burned skin with two different doses by histomorphometry and laser Doppler flowmetry. Thirdy six male adult Wistar rats with two burns created on the back using water vapor were divided into 3 groups. In the fractioned dose laser group (GF), the lesions were irradiated with 1 J/cm2 on days 1, 3, 8 and 10; in the single dose laser group (GU), the lesions were irradiated with 4 J/cm2 on day 1. On control group (GC) lesions were not irradiated. The blood flow was measured on days 1, 3, 8, 10, 15 and 21 and three animals per group were sacrificed in these moments. Irradiated groups showed a peak of new blood vessels formation on day 15 while for GC the peak was on day 21. At this moment, the number of vessels in GC was significantly higher than GF and GS. Regarding to blood flux, irradiated groups displayed a higher value than GC on day 8, though no significant differences were observed. These findings suggest that LILT may accelerate skin repair, however, no significant differences were observed between the studied doses.

Estudos de diagnóstico de vitalidade pulpar em dentes decíduos traumatizados, através da Fluxometria Laser Doppler (FLD), têm utilizado dentes tratados endodonticamente, porém o diagnóstico clínico é realizado em dentes necrosados. O objetivo deste estudo foi avaliar a FLD como teste de vitalidade pulpar em incisivos superiores decíduos traumatizados necrosados, desvitalizados (DES), antes e após tratamento endodôntico. Foram analisados em 57 crianças, de 40 a 85 meses de idade, valores de fluxo de dois dentes: IC DES - I VIT - 1 incisivo central necrosado (leitura antes e após a endodontia) e 1 incisivo central ou lateral vitalizado (leitura repetida em 2 sessões); I VIT - I VIT - 2 incisivos centrais ou laterais vitalizados (leitura em sessão única). Foi utilizado o Fluxômetro Laser Doppler (Moor Instruments, moorLab, Axminster, Inglaterra), diodo laser emitindo no comprimento de onda de 780nm, banda Doppler em 15kHz, sonda MP13 posicionada na vestibular a 4mm da margem gengival e estabilizada com posicionador de silicone. Foram avaliados dois parâmetros: F(UA), valor de fluxo de um único dente em unidades arbitrárias; F(%), variação percentual entre pares de dentes de um mesmo paciente. Estes parâmetros foram aplicados nos grupos antes e após a endodontia: F(UA) antes, F(UA) após, F(%) antes e F(%) após. No parâmetro F(UA), para os 29 IC DES antes, a variação de fluxo foi de 2,3 a 11,1UA, a média foi de 5,4UA e o desvio-padrão de 2,5UA. Para os 29 I VIT antes, a variação foi de 4,2 a 16,1UA (9,6 ± 3,5UA). Na segunda sessão, para os 29 IC DES após, foi de 1,3 a 7,4UA (3,4 ± 1,6UA), e para os 29 I VIT após foi de 3,6 a 19,7UA (9,3 ± 3,6UA). Para os 62 I VIT analisados em única sessão, a variação foi de 5,0 a 16,5UA (9,3 ± 2,4UA). No parâmetro F(%), para os 29 pares de IC DES antes - I VIT antes a variação foi de 28,0 a 98,1% (57,4 ± 17,2%). Para os 29 pares de IC DES após - I VIT após, de 18,0 a 84,5% (37,9 ± 15,2%). Para os 31 pares de I VIT - I VIT, foi de 57,5 a 146,5% (99,9 ± 23,3%). A performance dos parâmetros foi estimada pela área sob a curva ROC (AUC). Para F(UA) antes, a AUC foi de 0,862, para F(%) antes, a AUC foi de 0,941, para F(UA) após, a AUC foi de 0,975. Seus desempenhos, considerando intervalo de confiança de 95%, foram considerados entre moderadamente acurados e altamente acurados. Para F(%) após, a AUC foi de 0,987, sendo seu desempenho altamente acurado. Após comparação das AUCs, somente foi observada diferença significante, p=0,002, entre F(UA) antes e F(UA) após. Os pontos de corte propostos foram baseados nos dados obtidos antes da endodontia: para F(UA), valores menores ou iguais a 6,5UA classificam os dentes como desvitalizados e para F(%), valores menores ou iguais a 66,9%. Conclui-se que F(UA) e F(%) são parâmetros capazes de diferenciar dentes decíduos necrosados de dentes vitalizados, assim como de diferenciar dentes tratados endodonticamente de dentes vitalizados. / Studies on diagnosis of dental pulp necrosis in traumatized primary teeth using laser Doppler flowmetry (LDF) evaluate teeth with endodontic treatment; however, clinical diagnosis is performed in teeth with pulp necrosis. The aim of this study was to evaluate the LDF as pulp vitality test in traumatized primary upper incisors, with pulp necrosis (DES), before and after endodontic treatment. The pulpal flux values of 57 children, aged from 40 to 85 months, were evaluated: IC DES - I VIT - 1 central incisor with pulp necrosis (readings before and after endodontic treatment) and 1 vital central or lateral incisor (readings in 2 sessions); Control group: I VIT - I VIT - 2 vital incisors (readings in 1 session). The Laser Doppler Flowmeter (Moor Instruments, moorLab, Axminster, UK) was used. It is a diode laser emitting at 780 nm and bandwidth at 15 kHz. A MP13 probe was placed on the buccal surface of the tooth, 4mm from the gingival margin using silicone splints. Two parameters were evaluated: F(AU), the flux value of each tooth in arbitrary units, and F(%), the percentage variation of the flux value between pairs of teeth in the same patient. The two parameters were used before and after endodontic treatment: F(AU) before, F(AU)after, F(%) before and F(%) after. In the 29 IC DES before, F(AU) ranged from 2.3 to 11.1AU; the mean was 5.4AU and the standard deviation was 2.5AU; in the 29 I VIT before, ranged from 4.2 to 16.1AU (9.6 ± 3.5AU); in the 29 IC DES after, the values ranged from 1.3 to 7.4AU (3.4 ± 1.6AU), and in the 29 I VIT after, from 3.6 to 19.7AU (9.3 ± 3.6AU). In the 62 I VIT analyzed in one session, the values ranged from 5.0 to 16.5AU (9.3 ± 2.4AU). In respect to F(%), in the 29 pairs of IC DES before - I VIT before, the values ranged from 28.0 to 98.1% (57.4 ± 17.2%); in the 29 pairs of IC DES after - I VIT after, from 18.0 to 84.5% (37.9 ± 15.2%); in the 31 pairs of I VIT - I VIT, from 57.5 to 146.5% (99.9 ± 23.3%). The performance of both tests was estimated by the area under the ROC curve (AUC). Regarding F(AU) before, the AUC was 0.862; in F(%) before, the AUC was 0.941; in F(AU) after, the AUC was 0.975. The performances were classified between moderate and highly accurate (95% Confidence Interval). Regarding F(%) after, the AUC was 0.987 and its performance was highly accurate. Comparing the AUCs, there was statistical significance (p=0.002), between F(AU) before and F(AU) after. The cut-off values were based on data before endodontic treatment. The F(AU) values that were equal to or smaller than 6.5AU, and the F(%) values that were equal to or smaller than 66.9% classified the tooth as non-vital The two parameters studied, F(AU) and F(%), are able to distinguish non-vital primary teeth from vital teeth, and to distinguish vital teeth from teeth with endodontic treatment.

Hipertensos têm rarefação capilar e disfunção endotelial microcirculatória, tornando-se mais vulneráveis a lesões em órgãos-alvo. O estudo buscou avaliar o efeito de seis meses de tratamento farmacológico sobre densidade capilar e reatividade microvascular a estímulos fisiológicos e farmacológicos em hipertensos de baixo risco cardiovascular. Secundariamente testou-se a existência de diversidade nas respostas a diferentes estratégias anti-hipertensivas. Foram recrutados 44 pacientes, com 46,71,3 anos e 20 normotensos com 48,01,6 anos. Avaliaram-se dados antropométricos e laboratoriais e dosaram-se no soro o fator de crescimento vascular endotelial (VEGF), receptor Flt-1 para VEGF e óxido nítrico (NO). A contagem capilar foi por microscopia intravital, captando-se imagens da microcirculação no dorso da falange do dedo médio e contando os capilares com programa específico. Repetia-se o procedimento após hiperemia reativa pós-oclusiva (HRPO) para avaliar o recrutamento capilar. A reatividade vascular foi testada por fluxometria Laser Doppler, iontoforese de acetilcolina (Ach), HRPO e hiperemia térmica local (HTL). Os pacientes foram distribuídos aleatoriamente para dois grupos de tratamento: succinato de metoprolol titulado a 100 mg diários ou olmesartana medoxomila titulada a 40 mg diários, empregando-se, se necessário, a hidroclorotiazida. Os controles seguiram o mesmo protocolo inicial e após seis meses todos os testes foram repetidos nos hipertensos. As variáveis clínicas e laboratoriais basais eram semelhantes em comparação aos controles e entre os dois grupos de tratamento. Após seis meses, havia pequenas diferenças entre os grupos na relação cintura-quadril e HDL. A densidade capilar antes do tratamento era significativamente menor que no grupo controle (71,31,5 vs 80,61,8 cap/mm2 p<0,001 e HRPO 71,71,5 vs 79,52,6 cap/mm2 p<0,05) e, com o tratamento, aumentou para 75,41,1 cap/mm2 (p<0,01) no estado basal e para 76,81,1 cap/mm2 à HRPO (p<0,05). À reatividade vascular, a condutância vascular cutânea (CVC) em unidades de perfusão (UP)/mmHg era similar à HTL nos controles e hipertensos e aumentou com o tratamento nos dois subgrupos (metoprolol:1,730,2 a 1,900,2 p<0,001 e olmesartana:1,490,1 a 1,870,1 p<0,001). A CVC máxima à HRPO era menor nos hipertensos: 0,30(0,22-0,39) que nos controles: 0,39(0,31-0,49) com p<0,001. Após tratamento, aumentou para 0,41(0,29-0,51) com p<0,001. O aumento foi significativo apenas no grupo olmesartana (0,290,02 a 0,420,04 p<0,001). A diferença entre o tempo para atingir o fluxo máximo à HRPO aumentou no grupo metoprolol após tratamento 3,0 (-0,3 a 8,8) segundos versus olmesartana 0,4 (-2,1 a 2,4) segundos p<0,001. À iontoforese, a área sob a curva de fluxo (AUC) era similar nos grupos e aumentou com o tratamento, de 6087(3857-9137) para 7296(5577-10921) UP/s p=0,04. O VEGF e receptor não diferiam dos controles nem sofreram variações. A concentração de NO era maior nos hipertensos que nos controles: 64,9 (46,8-117,6) vs 50,7 (42-57,5) M/dl p=0,02 e não variou com tratamento. Em conclusão, hipertensos de baixo risco têm menor densidade e menor recrutamento capilar e ambos aumentam com tratamento. Apresentam também disfunção endotelial microcirculatória que melhora com a terapia. / Capillary rarefaction and microcirculatory endothelial dysfunction are hallmarks of hypertension, rendering patients vulnerable to target organ lesions. The study aimed at assessing the effect of a six-month treatment period upon capillary density and microvascular reactivity to physiological and pharmacological stimuli. In addition, two different treatment strategies were tested for possible differences between effects upon those variables. A total of 44 patients were recruited, mean age 46.71.3 years and 20 normotensive individuals served as controls, mean age 48.01.6 years. Anthropometrical and laboratory data were collected, as well as plasma levels of vascular endothelial growth factor (VEGF), its receptor Flt-1 and nitric oxide (NO). Capillary density was obtained by intra-vital microscopy of the dorsum of the middle phalanx before and after post-occlusive reactive hyperemia (PORH). Capillary loops were counted by a semi-automated software. Microvascular reactivity was tested by laser Doppler flowmetry (LDF), and the challenges consisted of acetylcholine iontophoresis, local thermal hyperemia (LTH) and PORH. Patients were randomly allocated to either one of two treatment arms: metoprolol succinate uptitrated to 100 mg daily or olmesartan medoxomil uptitrated to 40 mg daily, with addition of hydrochlorothiazide if necessary. Controls underwent the same initial protocol and all tests were repeated in patients after six months. Baseline clinical and laboratory parameters were similar between patients and controls and between the two treatment groups. After six months there were slight, although significant, differences between the two groups in waist/hip ratio and HDL-cholesterol. In the whole cohort, pretreatment capillary density was significantly reduced compared to controls (71.31.5 vs 80.61.8 cap/mm2 p<0.001 and PORH 71.71.5 vs 79.52.6 cap/mm2 p<0.05). After treatment it increased to 75.41.1 cap/mm2 (p<0.01) at rest and 76.81,1 cap/mm2 during PORH. During LTH, cutaneous vascular conductance (CVC) in perfusion units (PU)/ mmHg was similar in patients and controls and increased significantly in both subgroups (metoprolol: from 1.730.2 to 1.900.2 p<0,001 and olmesartan: from 1.490.1 to 1.870.1 p<0.001). Maximal CVC during PORH was reduced in hypertensive patients: 0.30 (0.22-0.39) compared to controls: 0.39(0.31-0.49) with p<0.001. After therapy it increased to 0.41(0.29-0.51) with p<0.001. The change was significant only for the olmesartan subgroup (from 0.290.02 to 0.420.04 p<0.001). After treatment, the difference in time spent to reach peak flow during PORH inreased significantly in patients taking metoprolol but not in those taking olmesartan: -3.0 (-8.8 to 0.2) and 0.4 (-2.1 to 2.4) seconds after vs before, respectively p<0,001. Area under the Ach iontophoresis flow curve (AUC) was similar in controls and hypertensive patients, and increased after treatment, from 6087 (3857-9137) to 7296 (5577-10921) PU/s p=0.04. VEGF and Flt-1 receptor were similar among all groups and did not change with treatment. NO levels were higher in hypertensive individuals than in controls: 64.9 (46.8-117.6) vs 50.7 (42.0-57.5) M/dl p=0.02 and did not change with treatment. In conclusion, low-risk hypertensive patients show reduced capillary density/recruitment, and endothelial microvascular dysfunction. Both improve with treatment