Intermittent hypoxia changes the interaction of the kinin-VEGF system and impairs myocardial angiogenesis in the hypertrophic heart.

Intermittent hypoxia (IH) is a feature of obstructive sleep apnea (OSA), a condition highly associated with hypertension-related cardiovascular diseases. Repeated episodes of IH contribute to imbalance of angiogenic growth factors in the hypertrophic heart, which is key in the progression of cardiovascular complications. In particular, the interaction between vascular endothelial growth factor (VEGF) and the kallikrein-kinin system (KKS) is essential for promoting angiogenesis. However, researchers have yet to investigate experimental models of IH that reproduce OSA, myocardial angiogenesis, and expression of KKS components. We examined temporal changes in cardiac angiogenesis in a mouse IH model. Adult male C57BI/6 J mice were implanted with Matrigel plugs and subjected to IH for 1-5 weeks with subsequent weekly histological evaluation of vascularization. Expression of VEGF and KKS components was also evaluated. After 3 weeks, in vivo myocardial angiogenesis and capillary density were decreased, accompanied by a late increase of VEGF and its type 2 receptor. Furthermore, IH increased left ventricular myocardium expression of the B2 bradykinin receptor, while reducing mRNA levels of B1 receptor. These results suggest that in IH, an unexpected response of the VEGF and KKS systems could explain the reduced capillary density and impaired angiogenesis in the hypoxic heart, with potential implications in hypertrophic heart malfunction.

Total renal denervation reduces sympathoexcitation to different target organs in a model of chronic kidney disease.

It is known that increased sympathetic nerve activity in chronic kidney disease (CKD) progressively worsens kidney function and hypertension. We tested the hypothesis that total renal denervation contributes to reduce sympathetic activation to different beds and improves renal function in 5/6 nephrectomy model of CKD in male Wistar rats. After eight weeks of 5/6 nephrectomy surgery there was an increase in mean arterial pressure (CKD 179±22mmHg, n=6 vs. control animals 108±9; p<0.05, n=6) with no changes in heart rate (HR). Sympathetic nerve activity was increased at different levels to the remaining kidney, splanchnic and lumbar beds compared to control (CTL) group (CKD rSNA: 150±50, n=9 vs. CTL 96±15, n=9; CKD sSNA: 129±51, n=5 vs. CTL 34±14, n=6; CKD lSNA: 203±35, n=8 vs. CTL 146±21, spikes/s, n=7, p<0.05). Three weeks after total renal denervation (DNX) MAP was normalized in the CKD rats (124±19mmHg, n=5, p<0.05), with no change in HR. The lSNA was normalized (151±40, n=5, vs. CKD 203±35 spikes/s, n=8) and sSNA was decreased in 49% (64±34, n=5 vs. CKD 129±51 spikes/s, n=5, p<0.05). Renal function, assessed by creatinine plasma levels was improved after renal denervation (CKD 1.50±0.64, n=8; vs. CKD+DNX 0.82±0.22mg/mL, n=8, p<0.05). These findings demonstrate that renal nerves contribute to the maintenance of hypertension in CKD by increasing sympathoexcitation to other beds.

Sleep restriction during pregnancy and its effects on blood pressure and renal function among female offspring.

The influence of sleep restriction (SR) during pregnancy on blood pressure and renal function among female adult offspring was investigated. Pregnant Wistar rats were distributed into control and SR groups. The SR was performed between the 14th and 20th days of pregnancy (multiple platforms method for 20 h/day). At 2 months of age, half of the offspring from both groups were subjected to an ovariectomy (ovx), and the other half underwent sham surgery. The groups were as follows: control sham (Csham), control ovx (Covx), SR sham (SRsham), and SR ovx (SRovx). Renal function markers and systolic blood pressure (BPi, indirect method) were evaluated at 4, 6, and 8 months. Subsequently, the rats were euthanized, kidneys were removed, and processed for morphological analyses of glomerular area (GA), number of glomeruli per mm3 (NG), and kidney mass (KM). Increased BPi was observed in the Covx, SRsham, and SRovx groups compared to Csham at all ages. Increased plasma creatinine concentration and decreased creatinine clearance were observed in the SRsham and SRovx groups compared to the Csham and Covx groups. The SRovx group showed higher BPi and reduced creatinine clearance compared to all other groups. The SRovx group showed reduced values of GA and KM, as well as increased NG, macrophage infiltration, collagen deposit, and ACE1 expression at the renal cortex. Therefore, SR during pregnancy might be an additional risk factor for developing renal dysfunction and increasing BP in female adult offspring. The absence of female hormones exacerbates the changes caused by SR.

Autonomic and Renal Alterations in the Offspring of Sleep-Restricted Mothers During Late Pregnancy

OBJECTIVES: Considering that changes in the maternal environment may result in changes in progeny, the aim of this study was to investigate the influence of sleep restriction during the last week of pregnancy on renal function and autonomic responses in male descendants at an adult age. METHODS: After confirmation of pregnancy, female Wistar rats were randomly assigned to either a control or a sleep restriction group. The sleep-restricted rats were subjected to sleep restriction using the multiple platforms method for over 20 hours per day between the 14th and 20th day of pregnancy. After delivery, the litters were limited to 6 offspring that were designated as offspring from control and offspring from sleep-restricted mothers. Indirect measurements of systolic blood pressure (BPi), renal plasma flow, glomerular filtration rate, glomerular area and number of glomeruli per field were evaluated at three months of age. Direct measurements of cardiovascular function (heart rate and mean arterial pressure), cardiac sympathetic tone, cardiac parasympathetic tone, and baroreflex sensitivity were evaluated at four months of age. RESULTS: The sleep-restricted offspring presented increases in BPi, glomerular filtration rate and glomerular area compared with the control offspring. The sleep-restricted offspring also showed higher basal heart rate, increased mean arterial pressure, increased sympathetic cardiac tone, decreased parasympathetic cardiac tone and reduced baroreflex sensitivity. CONCLUSIONS: Our data suggest that reductions in sleep during the last week of pregnancy lead to alterations in cardiovascular autonomic regulation and renal morpho-functional changes in offspring, triggering increases in blood pressure.

[Histomorphometric differences between the left and right internal thoracic arteries in humans]. / Diferenças histomorfométricas entre as artérias torácicas internas esquerda e direita em humanos.

OBJECTIVE: The use of the left internal thoracic artery in coronary artery bypass surgery is currently recognized as the best option, providing lesser incidence of cardiovascular events and superior long-term survival. As a result, great expansion of bilateral internal thoracic artery (ITAs) grafts has been observed, with additional demonstration of improved long-term survival. Therefore the aim of this study was to examine and compare the histomorphometric structure among different segments of the left and right ITA. METHOD: Specimens of ITAs harvested from 18 cadavers were divided in nine proportional segments. Cuts of each segment had been stained with hematoxylin-eosin and Verhoeff-Van Gieson technique. The following parameters had been analyzed: perimeter of the arterial lumen, thickness of the intima, thickness of the media layer and amount of elastic fiber in the media layer. RESULTS: The perimeter of both ATIs decreases downstream its course, the proximal segments of the right ITA exhibit perimeter significantly greater than left ITA The analysis of the intima thickness revealed no significant difference between left and right ITA, except in the segment 9. The thickness of media layer showed no statistical difference between them, except in the segment 1. The number of elastic layers in the distal left ITA segments is significantly higher than right ITA. CONCLUSION: Data analyses from this study suggest structural differences between the left and right internal thoracic arteries.

Diferenças histomorfométricas entre as artérias torácicas internas esquerda e direita em humanos / Histomorphometric differences between the left and right internal thoracic arteries in humans

OBJETIVO: O uso do enxerto de artéria torácica interna esquerda (ATIE) é atualmente reconhecido como a melhor opção na cirurgia de revascularização miocárdica, proporcionando menor incidência tardia de eventos cardiovasculares e maior sobrevida. Conseqüentemente, houve grande incremento nas últimas décadas do uso bilateral das artérias torácicas internas (ATIs), com demonstração de melhora adicional de sobrevida em longo-termo. O objetivo desse trabalho foi estudar a estrutura histológica das ATIs esquerda e direita (ATID), com a análise histomorfométrica seqüencial e comparativa entre os segmentos das duas artérias. MÉTODOS: Foram estudados espécimes de ATIs retirados de 18 cadáveres, divididos em nove segmentos proporcionais. Cortes de cada segmento foram corados com técnica de hematoxilina-eosina e Verhoeff-Van Gieson. Foram analisados os seguintes parâmetros: perímetro da luz arterial, espessura da íntima, espessura da camada média e quantidade de fibras elásticas da camada média. RESULTADOS: O perímetro interno de ambas as ATIs diminuiu ao longo do percurso, dos segmentos mais proximais para os mais distais. Os segmentos proximais da ATID apresentaram perímetro significativamente maiores do que os da ATIE. A análise da espessura da íntima revelou não existir diferença significativa entre ATIE e ATID, exceto no segmento 1. A espessura da camada média diminuiu ao longo da extensão das ATIs, não havendo diferença estatística entre elas, exceto no segmento 9. O número de lâminas elásticas nos segmentos distais da ATIE foi estatisticamente superior ao da ATID. CONCLUSÃO: Portanto, os dados do presente estudo sugerem haver diferenças estruturais entre as ATIs direita e esquerda.

OBJECTIVE: The use of the left internal thoracic artery in coronary artery bypass surgery is currently recognized as the best option, providing lesser incidence of cardiovascular events and superior long-term survival. As a result, great expansion of bilateral internal thoracic artery (ITAs) grafts has been observed, with additional demonstration of improved long-term survival. Therefore the aim of this study was to examine and compare the histomorphometric structure among different segments of the left and right ITA. METHOD: Specimens of ITAs harvested from 18 cadavers were divided in nine proportional segments. Cuts of each segment had been stained with hematoxylin-eosin and Verhoeff-Van Gieson technique. The following parameters had been analyzed: perimeter of the arterial lumen, thickness of the intima, thickness of the media layer and amount of elastic fiber in the media layer. RESULTS: The perimeter of both ATIs decreases downstream its course, the proximal segments of the right ITA exhibit perimeter significantly greater than left ITA The analysis of the intima thickness revealed no significant difference between left and right ITA, except in the segment 9. The thickness of media layer showed no statistical difference between them, except in the segment 1. The number of elastic layers in the distal left ITA segments is significantly higher than right ITA. CONCLUSION: Data analyses from this study suggest structural differences between the left and right internal thoracic arteries.

Estudo histomorfométrico seqüencial da artéria torácica interna esquerda / Sequential histomorphometric study of the left internal thoracic artery

OBJETIVO: O uso de enxertos de artéria torácica interna esquerda (ATIE) é atualmente reconhecido como a melhor opção na cirurgia de revascularização miocárdica, proporcionando menor incidência de eventos cardiovasculares e maior sobrevida. Entretanto, com a expansão do uso dos enxertos arteriais, faz se necessário melhor entendimento da estrutura histológica da ATIE. Portanto, o objetivo deste trabalho foi estudar a estrutura histológica da ATIE e a análise histomorfométrica seqüencial e comparativa entre os diferentes segmentos. MÉTODO: Foram estudados espécimes de ATIE retirados de 18 cadáveres, divididos em nove segmentos proporcionais. Cortes de cada segmento foram corados com técnica de Verhoeff-Van Gieson. Foram analisados os seguintes parâmetros: perímetro da luz arterial, espessura da íntima, espessura da camada média, número de fibras elásticas da camada média e a densidade de fibras elásticas. RESULTADOS: Os dados obtidos mostraram que perímetro da ATIE mostra tendência a diminuir ao longo de sua extensão, a espessura da íntima é aumentada nos segmentos proximais, a espessura da camada média diminui ao longo de sua extensão, o número de lâminas elásticas se concentra nos segmentos intermediários, a densidade de lâminas elásticas é diminuída nos segmentos proximais e distais. CONCLUSÃO: Portanto, os achados do presente estudo confirmam a heterogeneidade da estrutura histológica seqüencial da ATIE.

OBJECTIVE: The use of left internal thoracic artery (LITA) in coronary artery bypass surgery is currently recognized as the best option, providing lower incidences of cardiovascular events and superior long-term survival. Now, incremental utilization of these grafts makes a reassessment of its histological structure necessary. Therefore, the purpose of this study was to examine and compare the sequential histological structure of LITA. METHOD: Specimens of LITA harvested from 18 cadavers, divided into nine proportional segments, were studied. Cuts of each segment were stained by the Verhoeff-Van Gieson technique. The following parameters were analyzed: perimeter of the arterial lumen, thickness of the intima, thickness of the media layer, amount of elastic fiber in the media layer and the elastic fiber density. RESULTS: The collected data showed that perimeter of the LITA decreases downstream on its course, the thickness of the intima is increased in the proximal segments, the thickness of the media layer diminishes throughout its extension, the number of elastic fibers is concentrated in the intermediate segments and the density of elastic fibers is reduced in the proximal and distal segments. CONCLUSION: Therefore, the findings of the present study validate the heterogeneity of the LITA sequential histological structure.