Accelerated progression of arterial stiffness in dialysis patients compared with the general population

BACKGROUND/AIMS: The aim of this study was to compare the progression of aortic stiffness in chronic hemodialysis patients (CHP) with that of general population patients (GPP) over a 36-month period and to evaluate the determinants of this progression. METHODS: The study group included 80 patients undergoing hemodialysis (aged 59.3 +/- 11.8 years; duration of dialysis 5.47 +/- 5.16 years). The control group consisted of 60 patients (aged 57.5 +/- 10.9 years) with a glomerular filtration rate of > 60 mL/min/1.73 m2. Pulse wave velocity (PWV) was determined from time diversity propagation of the common carotid artery and femoral artery by Doppler ultrasound. Clinical and biochemical parameters were determined in serum using standard laboratory procedures. RESULTS: The mean PWV values at baseline and 36 months were 11.18 +/- 2.29 and 11.82 +/- 2.34 m/sec in the CHP group, and 9.02 +/- 1.89 and 9.29 +/- 1.93 m/sec in the GPP group, respectively. The average PWV progressions were 63.95 +/- 18.373 cm/sec in CHP and 27.28 +/- 28.519 cm/sec in GPP. By multiple regression analysis, hemoglobin (standardized coefficient beta [betast] = -0.405, p = 0.004; betast = -0.364, p = 0.011), albumin (betast = -0.349, p = 0.042; betast = -0.303, p = 0.034), CRP (betast = 0.458, p = 0.002; betast = 0.187, p = 0.008), and total cholesterol (betast = 0.236, p = 0.038; betast = 0.171, p = 0.078) were independently associated with PWV in the CHP and GPP groups, respectively. CONCLUSIONS: Accelerated arterial stiffness was more pronounced in the CHP group than in the GPP group. The independent determinants of this progression in both groups include traditional risk factors and blood levels of hemoglobin, albumin and CRP. Cholesterol and uremia-related factors are determinants only in CHP.

Expresión de ICAM-1 en el endotelio de arterias humanas mediante inmunohistoquímica / ICAM-1 Expression in endothelium of human arteries by immunohistochemistry

Las enfermedades cardiovasculares son la principal causa de muerte a nivel mundial. Entre ellas tienen gran relevancia las de tipo isquémicas, en donde el desarrollo de placas ateroscleróticas es el proceso fisiopatológico central. El estudio de la aterosclerosis es fundamental para comprender como se inicia este proceso patológico y los factores que influyen en su desarrollo. Distintas metodologías de laboratorio, entre otras la inmunohistoquímica, permiten reconocer las células y moléculas que participan en el proceso ateromatoso y que van interactuando según la progresión de la lesión. Un marcador de disfunción endotelial es la mayor expresión de la molécula de adhesión intercelular ICAM-1. En este trabajo se realizó la estandarización de inmunohistoquímica para la molécula de adhesión ICAM-1, y se estudió su expresión en arterias humanas sanas y con placa ateromatosa. En las muestras de arterias humanas con patología aterosclerótica, la expresión de ICAM-1 se observó aumentada, pero fue de difícil reconocimiento. Esto principalmente porque el tejido empleado como control en la estandarización fue una amígdala con hiperplasia y proceso inflamatorio que aumenta notablemente la expresión de ICAM-1. La implementación del método de inmunohistoquímica para ICAM-1 en arterias humanas permitirá conocer estados de disfunción endotelial y el desarrollo futuro del diseño e implementación de métodos de diagnóstico en aquellos procesos ateroclerótico en estado incipiente.

Cardiovascular diseases (CVD) are the leading cause of death in the world. Among them the ischemic type are of great importance, where the development of atherosclerotic plaques is the central pathophysiological process. The study of atherosclerosis is critical to understand how this disease process begins and factors influencing its development. Various laboratory methods, including immunohistochemistry, allow the recognition of cells and molecules involved in the atheromatous process that are interacting according to the progression of the lesion. A marker of endothelial dysfunction is the increased expression of intercellular adhesion molecule ICAM-1. In this paper, an immunohistochemistry method was standardized for the adhesion molecule ICAM-1, and its expression was studied in healthy human arteries with atheromatous plaque. In samples of human arteries with atherosclerotic disease, the expression of ICAM-1 was observed to be increased, but was hardly recognizable. This mainly because the tissue used as a control for standardization was a tonsil with an inflammatory process and hyperplasia, which significantly increases the expression of ICAM-1. The implementation of the immunohistochemistry method for ICAM-1 in human arteries will reveal endothelial dysfunction states that will enable a future design and implementation of methods of diagnosis in atherosclerotic processes in the early stages.

Systematization, distribuiton and Territory of the rostral cerebral artery on the brain surface in chinchilla

The present study has analyzed thirty chinchilla (Chinchilla lanigera) brains, injected with latex, aiming tosystematize and describe the distribution and the vascularization territories of the rostral cerebral artery. Therostral cerebral artery was the terminal branch of the terminal branch, right and left, of the basilar artery,projected from the emittion of the middle cerebral artery, rostromedially, crossing dorsally the optic nerve untilit reaches the cerebral longitudinal fissure, ventrally. Its branches were distributed mostly on the paleopallium,supplying the olfactory trigone, the medial olfactory tract, the olfactory peduncle and the olfactory bulb.The branches to the neopallium vascularized the entire medial surface, except for the tenctorial part of it, thefrontal pole and a zone that was extended from the frontal to the occipital poles, medially to the vallecula,on the convex surface of the cerebral hemisphere. The first collateral branch of the rostral cerebral artery wasthe medial branch, which entered into the longitudinal fissure of the brain and continued as rostral interhemisphericartery. The rostral cerebral artery continued rostrally emitting central branches and the medialand lateral arteries of the olfactory bulb, to the paleopallial region of the chinchilla brain. After the emittion ofthe medial artery of the olfactory bulb, the rostral cerebral artery continued to follow the cerebral longitudinalfissure, as internal ethmoidal artery, its terminal branch.

The Relationship between Aldosterone to Renin Ratio and RI Value of the Uterine Artery in the Preeclamptic Patient vs. Normal Pregnancy

PURPOSE: Plasma levels of renin, angiotensin II and aldosterone are increased during normal pregnancy. However, these values in preeclampsia are decreased to nearly that of a nonpregnant subject, and vascular sensitivity to angiotensin II is increased. In preeclampsia, aldosterone is decreased less than rennin. Therefore current studies were undertaken to determine the relationship between aldosterone to renin ratio (ARR) and uterine artery perfusion via RI value. MATERIALS AND METHODS: In this study, the relationship between plasma aldosterone and renin concentration was determined in 27 preeclamptic women and 50 normal pregnant women, whose gestational weeks were matched. The aldosterone to renin ratio was calculated and compared between the two groups. Doppler velocimetry of the uterine artery, which was used to calculate resistance index (RI), was performed on all subjects. The relationship between ARR and RI value was reviewed. RESULTS: In the preeclampsia group, RI value of the uterine artery was significantly higher than that of normal pregnant women. Both plasma renin and aldosterone concentrations were lower in the preeclampsia group. However, the ratio of these two parameters was significantly higher (38.3 vs. 16.1, p < 0.001); the greater ARR, the higher the RI of the uterine artery (r(2)=0.053, p=0.048). CONCLUSION: This study demonstrates that a high aldosterone to renin ratio may have a negative effect on perfusion of the uterine artery and play an important role in the pathophysiology of preeclampsia.

15-Deoxy-delta 12,14-ProstaglandinJ2 Regulates Dedifferentiation through Peroxisome Proliferator-Activated Receptor-gamma-Dependent Pathway but Not COX-2 Expression in Articular Chondrocytes

Peroxisome proliferator-activated receptors-gamma (PPAR-gamma) is critical for phenotype determination at early differentiation stages of mesenchymal cells, whereas its physiological role is unclear. Therefore, we investigated the role of 15-deoxy-delta 12,14-prostaglandinJ2 (15d-PGJ2), the natural receptor ligand for PPAR-gamma, on dedifferentiation and inflammatory responses, such as COX-2 expression and PGE2 production, in articular chondrocytes. Our data indicate that the 15d-PGJ2 caused a loss of differentiated chondrocyte phenotype as demonstrated by inhibition of type II collagen and proteoglycan synthesis. 15d-PGJ2 also induced COX-2 expression and PGE2 production. The 15d-PGJ2-induced dedifferentiation effect seems to be dependent on PPAR-gamma activation, as the PPRE luciferase activity increased and PPAR-gamma antagonist, BADGE, abolished type II collagen expression. However, BADGE did not block 15d-PGJ2-induced COX-2 expression. Collectively, our findings suggest that PPAR-gamma-dependent and -independent mechanisms of 15d-PGJ2-induced dedifferentiation and inflammatory responses in articular chondrocytes, respectively. Additionally, these data suggest that targeted modulation of the PPAR-gamma pathway may offer a novel approach for therapeutic inhibition of joint tissue degradation.

Influence of 7beta-hydroxycholesterol on glutathione status and nitric oxide production in macrophages: in vitro studies.

Incubation of murine peritoneal macrophages with 7beta-hydroxycholesterol (7beta-OH) for 24 hr led to dose-dependent reduction in cellular glutathione content as well as nitrite levels in the medium. Treatment with an inorganic form of selenium, sodium selenite which is a potent antioxidant, elevated the cellular glutathione levels and decreased nitrite levels. Our results suggest that 7beta-OH may exert its pro-atherogenic effect by inhibiting glutathione synthesis and nitric oxide production by macrophages present in the arterial wall and thus, impair the cellular antioxidant defense system.

Characteristics of Ca2+ release mechanisms from an intracellular Ca2+ store in rabbit coronary artery

To elucidate the Ca2+ release mechanisms in the rabbit coronary artery, arterial preparations were permeabilized with beta-escin and changes in tension were measured under varying experimental conditions. Additionally, we investigated properties and distribution of two kinds of Ca2+ release mechanisms, Ca2+-induced Ca2+ release (CICR) and IP3-induced Ca2+ release (IICR). The results obtained were summarized as follows; 1. When a rabbit coronary artery was incubated in a relaxing solution containing 30 microM beta-escin for 40 min. sensitivity to externally added Ca2+ was much higher in beta-escin permeabilized muscle than in intact preparations. The contractile effect of IP3 in beta-escin permeabilized muscle was also demonstrated; 2. Caffeine and IP3 contracted coronary arteries were permeabilized with beta-escin, but the amplitude of contraction was much larger in the presence of caffeine than of IP3. 3. Intracellular heparin completely inhibited the contractions induced by IP3, but not those by caffeine. On the other hand, procaine inhibited the responses to caffeine, but not those to IP3. Ryanodine inhibited both the caffeine- and IP3-induced contractions. 4. The amplitude of contractile responses was much larger to the maximal stimulation of CICR by applying caffeine than to the maximal stimulation of IICR by applying IP3. After the maximal CICR stimulation by caffeine, the activation of IICR by IP3 without the reloading of Ca2+ could no longer evoke contraction. On the other hand, after the maximal IICR activation, the activation of CICR could still evoke contraction although the amplitude of the contraction was smaller when compared with the case without the initial IICR stimulation. 5. Acetylcholine contracted coronary artery smooth muscles were permeabilized with beta-escin. However, in the absence of added guanosine triphosphate (GTP), the responses were very small. Acetylcholine-induced contraction was inhibited by heparin, but not by procaine. From the above results, it may be concluded that there are two kinds of mechanisms of Ca2+ release, CICR and IICR, in the rabbit coronary artery smooth muscle cell. Also, whereas the CICR mechanism distributes on the membrane of the whole smooth muscle Ca2+ store, the IICR mechanism distributes only on a part of it.

Changes in intracellular Ca2+ concentration of rabbit coronary artery smooth muscle cell during ischemic cardioplegic period

To elucidate the possibility whether an elevation of intracellular Ca2+ concentration ([Ca2+]i) in rabbit coronary artery myocytes during ischemic cardioplegic period may serve as one of the mechanisms of the "no-reflow' phenomenon or not, the changes in [Ca2+]i were measured under ischemic cardioplegia conditions using a fluorescent Ca2+ indicator, fura 2/AM. When single cells were perfused with cardioplegic or ischemic cardioplegic solutions, [Ca2+]i was significantly increased and the degree of [Ca2+] elevation was further augmented by the ischemic cardioplegic solution. Pretreatment of a sarcoplasmic reticulum emptying agent, 20 mM caffeine, had no effect on ischemic cardioplegia-induced [Ca2+]i changes, but application of a Ca2+ channel blocker, 5 x 10 (-1)M nifedipine, or an antagonist of Na+/Ca2+ exchange, 5 mM Ni2+, significantly inhibited the [Ca2+]i elevation, respectively. The magnitude of ischemic cardioplegia-induced [Ca2+]i elevation was dependent on the Ca2+ concentration of perfusate in the range of 0 and 25 mM. When Ni2+ was added to the reperfusion solution, recovery of ischemic cardioplegia-induced [Ca2+]i elevation was very rapid compared with the controls. It is concluded that ischemic cardioplegia-induced [Ca2+]i elevation may serve as one of the mechanisms of the "no-reflow' phenomenon in rabbit coronary artery smooth muscle cells. We propose that Na+/Ca2+ exchange may serve as a key function in ischemic cardioplegia-induced [Ca2+]i elevation.

Vascular prostacyclin production in andean women with pregnancy-induced hypertension

Although prostacyclin (PGI2) production in the umbilical artery is known to be reduced in prognancy-induced hypertension (PIH), little information is available about its production in maternal vascular tissues. We measured 6-keto-prostaglandin F 1* generation in the umbiblical and comentum arteries of 24 Andean women divided into three groups: 1) 8 normal pregnant women, 2) 8 cases with clinical evidence of severe PIH, and 3) 8 normotensive non-pregnant women.The normal pregnant group (232 ñ 172 pg mg-1 2h-1) and the non-pregnant control group (237 ñ 146 pg mg-1 2h-1 0 showed similar PGI2 production in the omentum arteries, whereas the PIH group showed lower PGI2 generation (P<0.05) than the normal patients both in the umbilical (697 ñ 377 vs 1528 ñ 291 pg mg-1 2h-1) and omentum (132 ñ 73 vs 232 ñ 172 pg mg-1 2h-1) arteries. PGI2 production was 6.8 times lower in the omentum arteries than in the umbilical arteries. The data confirm and extend the view of the occurrence of reduced PGI2 production in the maternal-fetal vascular tissues of women with severe PIH.

Depositos de calcio sensibles a la noradrenalina en arterias de la cola de ratas normotensas y espontaneamente hipertensas: efectos de la rianodina y cafeina / Norepinephrine sensitive calcium pools in tail arteries of normotensiol and spontaneous hypertensive rats: effects of ryanodine and caffeine

Se estudiaron los efectos de la Rianodina (RI) y cafeína (CF) sobre las contracciones inducidas por noradrenalina (NA) en arterias de la cola de ratas espontáneamente hipertensas (SHR) y normotensas (WKY). El depósito intracellular de calcio sensible a NA fue vaciado completamente por exposición a NA 1 µM en solución libre de calcio, y fue responsable de un 40% de la contracción a NA en presencia de calcio 1.6 mM. Sin embargo, solamente en 60% del depósito fue utilizado para la contracción en calcio 1.6 mM. La reexposición al calcio extracelular rellenó el depósito sensible a NA en menos de 10 minutos, pero mientras el depóstio de la WKY captó aproximadamente el mismo calcio que tenía previamente (a juzgar por la magnitud de la respuesta mecánica posterior en solución libre de calcio), la SHR captó aproximadamente el doble de calcio en las msmas condiciones. La RI impidió el relleno del depósito en la SHR y WKY, sin liberar calcio del depósito y sin afectar el influjo de calcio a través de la membrana. La CF también previno el relleno de los depósitos sensibles a NA, pero también liberó calcio del depósito y promovió el ingreso de calcio a través de la membrana celular. Se concluye que la principal acción de la RI em el músculo liso de la cola de la rata es prevenir la captación de calcio por el depósito intracelular sensible a NA, mientras que la CF tiene varios efectos: inhibición de la captación de calcio por el depósito, liberación de calcio por depóstio, y apertura de canales de calcio de la membrana celular. Además, en la SHR (pero no en la WKY) la pérdida de calcio de la membrana vuelve a ésta más permeable al calcio, permitiendo una captación aumentada de calcio por el depósito intracelular en una subsiguiente exposición al calcio extracelular