An interaction of renin-angiotensin and kallikrein-kinin systems contributes to vascular hypertrophy in angiotensin II-induced hypertension: in vivo and in vitro studies.

The kallikrein-kinin and renin-angiotensin systems interact at multiple levels. In the present study, we tested the hypothesis that the B1 kinin receptor (B1R) contributes to vascular hypertrophy in angiotensin II (ANG II)-induced hypertension, through a mechanism involving reactive oxygen species (ROS) generation and extracellular signal-regulated kinase (ERK1/2) activation. Male Wistar rats were infused with vehicle (control rats), 400 ng/Kg/min ANG II (ANG II rats) or 400 ng/Kg/min ANG II plus B1 receptor antagonist, 350 ng/Kg/min des-Arg(9)-Leu(8)-bradykinin (ANGII+DAL rats), via osmotic mini-pumps (14 days) or received ANG II plus losartan (10 mg/Kg, 14 days, gavage - ANG II+LOS rats). After 14 days, ANG II rats exhibited increased systolic arterial pressure [(mmHg) 184 ± 5.9 vs 115 ± 2.3], aortic hypertrophy; increased ROS generation [2-hydroxyethidium/dihydroethidium (EOH/DHE): 21.8 ± 2.7 vs 6.0 ± 1.8] and ERK1/2 phosphorylation (% of control: 218.3 ± 29.4 vs 100 ± 0.25]. B1R expression was increased in aortas from ANG II and ANG II+DAL rats than in aortas from the ANG II+LOS and control groups. B1R antagonism reduced aorta hypertrophy, prevented ROS generation (EOH/DHE: 9.17 ± 3.1) and ERK1/2 phosphorylation (137 ± 20.7%) in ANG II rats. Cultured aortic vascular smooth muscle cells (VSMC) stimulated with low concentrations (0.1 nM) of ANG II plus B1R agonist exhibited increased ROS generation, ERK1/2 phosphorylation, proliferating-cell nuclear antigen expression and [H3]leucine incorporation. At this concentration, neither ANG II nor the B1R agonist produced any effects when tested individually. The ANG II/B1R agonist synergism was inhibited by losartan (AT1 blocker, 10 µM), B1R antagonist (10 µM) and Tiron (superoxide anion scavenger, 10 mM). These data suggest that B1R activation contributes to ANG II-induced aortic hypertrophy. This is associated with activation of redox-regulated ERK1/2 pathway that controls aortic smooth muscle cells growth. Our findings highlight an important cross-talk between the DABK and ANG II in the vascular system and contribute to a better understanding of the mechanisms involved in vascular remodeling in hypertension.

Exercise training restores hypertension-induced changes in the elastic tissue of the thoracic aorta.

BACKGROUND/AIMS: Pharmacological antihypertensive therapies decrease both wall hypertrophy and collagen, but are unable to diminish the elastic content in the thoracic aorta. We investigated the effects of exercise training on aortic structure and function. METHODS: Spontaneously hypertensive rats (SHR) and normotensive rats (WKY), submitted to low-intensity training (T) or kept sedentary (S), were subjected to haemodynamic analyses. The thoracic aorta was processed for real-time PCR, light (morphometric/stereological evaluations) and electron microscopy. RESULTS: SHR(S) versus WKY(S) exhibited a higher heart rate, pressure and pulse pressure, increased α-actin, elastin and collagen mRNA expression, augmented wall volume and cross-sectional area (marked elastin/collagen content). In the SHR, training reduced pressure and heart rate, with slight reduction in pulse pressure. SHR(T) aortas exhibited small morphometric changes, reduced α-actin, elastin and collagen mRNA expression, normalization of increased elastic content, reduction in collagen/connective tissue and a decrease in smooth muscle cell volume (p < 0.05 for all comparisons). SHR(T) aortas showed improved circumferential orientation of smooth muscle cells and prevention of rupture/duplication of internal elastic lamina. No effects were observed in trained WKY aortas. CONCLUSIONS: Training effectively corrects elastic, collagen and smooth muscle content in SHR aortas. These changes, by reducing aortic pulsatility, facilitate a buffering function and reduce the cardiovascular risk.

Histomorfometria das meninges encefálicas de ratos Wistar em diferentes faixas etárias / Histomorphometry of encephalic meninges of Wistar rats in different bands

O desenvolvimento do sistema nervoso é bastante complexo, existindo poucos estudos sobre a organização dos envoltórios cerebrais relacionados ao crescimento encefálico. Utilizando como modelo experimental o rato, analisaram-se os diferentes aspectos estruturais e morfométricos da paquimeninge e leptomeninge durante o processo de envelhecimento. Foram utilizados quatro grupos de ratos em diferentes faixas etárias e analisadas as meninges em microscopias de luz e eletrônica. Verificamos que o grupo de ratos adultos apresentou uma maior área de fibras colágenas tanto do tipo I e quanto do tipo III, em relação aos outros grupos. Encontramos também que as fibras colágenas do tipo III em todos os grupos analisados ocupam uma maior área quando comparados com as fibras do tipo I. Os resultados revelam que a coloração de Weigert Oxona, que mostra fibras elásticas, elaunínicas e oxitalânicas, apresentou uma diferença estatisticamente maior de fibras quando comparados com as colorações de Weigert e Verhoeff, que mostra fíbras elaunínicas e elásticas, respectivamente. Os resultados ultra-estruturais demonstraram a presença de muitos fibroblastos e mitocôndrias tanto na paquimeninge como nas leptomeninges dos grupos de ratos neonatos e adultos, indicativo de alta atividade celular e conseqüentemente, intensa formação de tecido conjuntivo. Como as fibras colágenas do tipo III atuam na manutenção da estrutura de tecidos delicados e expansíveis, o estudo mostra que as funções das meninges encefálicas não estão relacionadas apenas com a resistência a trações e tensões a que estão sujeitas o encéfalo. Mas também a função relacionada com a distensibilidade dos vasos meníngeos e cerebrais de acordo com a necessidade do aporte sanguíneo em diversas funções específicas regionais do tecido nervoso.

The development of the nervous system is very complex and there are few studies about the organization of the brain envoltories related to the encephalus growing. Using the rat as an animal model, it was proposed to evaluate the several structural aspects of paquimeninge and leptomeninge in different ages. It was used 4 groups of different ages and processed according to the techniques of the light and transmission microscopy. It was verified that the adult rats present a higher area of collagen fibers of type I and III, if compared to the others groups. It was found that, the collagen fibers of type III occupy, in all analyzed groups, a higher area when compared to type I fibers. The results reveal that the Weigert Oxona's staining, which shows elastics, elauninics, and oxitalanics fibers, showed a statistically difference when compared to the Weigert's staining and Verhoeff's staining that show elauninics and elastics fibers, respectively. The ultra-structural aspects demonstrated the presence of many fibroblasts and mitochondria in the paquimeninge and also in the leptomeninges of the neonats and adults groups, indicating the high cellular activity and consequently, an intense formation of conjunctive tissue. As collagen fibers of type III acting on the structural maintenance of delicate and expansive tissues, the study shows that the function of the encephalic meninges are not only related to the to resistance to tractions and tensions that the encephalus is subjected. But also the function related to the distensibility of the meningeos and brain vases according to the sanguineous apport in several specific functions of the nervous system.

O ensino da anatomia: uma visäo discente / Teaching anatomy: a student view

Este trabalho visa contribuir para discussao da remodelacao de curriculos, especificamente das disciplinas de Anatomia, integrantes do Ciclo Basico do Curso de Medicina da Universidade de Sao Paulo. Apoiando-se em pesquisa de opiniao dos discentes, busca se estabelecer, de modo comparativo a concepcao dos docentes, indicadores objetivos para melhoria das atividades de ensino daquelas disciplinas

Microscopic anatomy of the human vertebro-basilar system

Os autores estudaram a disposiçäo dos componentes fibromusculares da parede das artérias vertebrais em seus segmentos terminais e a artéria basilar, usando os seguintes métodos de coloraçäo: Azan modificado por Heidenheim, resorcina-fucsina de Weigert e Weigert modificado por van Gieson. O sistema vértebro-basilar apresentou em sua parede estrutura mista, muscular e elástica, pela qual os vasos se adaptam às condiçöes circulatórias específicas daquela regiäo. Desta forma, as artérias vertebrais apresentam na camada mais externa da túnica média uma lâmina elástica limitante externa evidente, ao contrário do encontro na artéria basilar. Neste vaso, o tecido elástico se encontra principalmente na camada média, distribuindo-se de maneira heterogênea nos segmentos estudados, ou seja, no segmento caudal as fibras elásticas se dispöem predominantemente na camada mais interna da túnica média e, no segmento cranial, o componente elástico se dispöe homogeneamente em toda a camada média