Papel de la agiotensina II en el desarrollo aterosclerótico: efecto de su bloqueo / Role of angiotensin II in the development of atherosclerosis: effect of blockade

La angiotensina II, el principal efector del sistema renina-angiotensina, ejerce un papel importante en la génesis y en las complicaciones de la aterosclerosis. La angiotensina II estimula la producción de especies reactivas de oxígeno en el vaso que desempeñan un papel clave en la disfunción endotelial y en la oxidación de las lipoproteínas de baja densidad (LDL). Asimismo, este péptido participa en la inducción de la respuesta inflamatoria en la pared vascular mediante la producción de moléculas de adhesión y citoquinas quimiotácticas y proinflamatorias. La angiotensina II, además, estimula la proliferación y migración de células de músculo liso y modula el cambio fenotípico de las mismas dando lugar a un aumento de la síntesis de la matriz extracelular. Finalmente, la angiotensina II también participa en las complicaciones de la aterosclerosis al favorecer la ruptura de la placa y trombogenicidad de la misma. En consecuencia, el sistema renina-angiotensina desempeña un papel clave en la patofisiología de la aterosclerosis, por lo que su bloqueo ejercerá un efecto beneficioso sobre el desarrollo aterosclerótico previniendo las alteraciones trombóticas asociadas a él (AU)

Localization and quantitation of angiotensin AT1 and AT2 receptors in the pregnant and non-pregnant sheep uterus.

The two angiotensin II receptor subtypes, AT1 and AT2, have been reported to be differentially expressed in the myometrial membrane preparations of nulliparous and pregnant sheep, however, their distribution in the sheep reproductive tract has not been reported. The aim of this study is to map the distribution of AT1 and AT2 receptors in the anoestrus reproductive tract of the sheep by quantitative in vitro autoradiography and to investigate if the density and distribution of the receptors change during pregnancy. The AT2 receptor is abundant in a discrete layer in the myometrium of the anoestrus sheep uterus, whilst the AT1 receptor is expressed at lower levels, predominantly in the endometrium. Near-term pregnant uteri, show a marked change in the expression of angiotensin II receptors: the myometrium no longer expresses detectable AT2 receptors but rather, expresses low levels of AT1 receptors. Angiotensin converting enzyme is found in high concentrations in the blood vessels of the pregnant and non-pregnant sheep reproductive system and on the epithelial cells of the fallopian tubes of the non-pregnant sheep. These studies reveal marked reciprocal changes of angiotensin II receptors, with myometrial AT1 receptors increasing during pregnancy, whilst AT2 receptors fall markedly. These changes suggest that angiotensin II may be involved in regulating changes of uterine structure and function during pregnancy by interaction with multiple receptor subtypes.

Application of the fast-evaporation sample preparation method for improving quantification of angiotensin II by matrix-assisted laser desorption/ionization.

The fast-evaporation method of sample preparation has been applied for quantitative analysis using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. An instrumental protocol focusing on improvement of shot-to-shot repeatability and compensation for signal degradation has been developed for quantification of angiotensin II using the fast-evaporation technique and an internal standard. The fast-evaporation method was compared to the standard method of sample preparation (using a multicomponent matrix) in the quantitative analysis of angiotensin II, and found to be superior in several respects. Improvement in sample homogeneity using the fast-evaporation method enhanced both point-to-point repeatibility and sample-to-sample reproducibility. The relative standard deviations of the analyte/internal standard ratios (point RSD) were decreased by a factor of three compared to those obtained using the multicomponent matrix method. The average point RSD was found to be ca. 5% for the fast-evaporation technique. Two internal standards were evaluated for quantification of angiotensin II. The better one, 1-SAR-8-Ile angiotensin II, yielded a relative standard deviation of the standard curve slope of ca. 2.2% over two orders of magnitude of concentration (45 nM to 3000 nM), an improvement by a factor of two over the standard preparation method. Renal microdialysate samples, spiked with angiotensin II and the internal standard 1-SAR-8-Ile angiotensin II, were also analyzed using the fast-evaporation technique. The detection limit was calculated to be in the high attomole range (675 amol). Furthermore, the accuracy for a single determination of angiotensin II concentration in these samples was found to be 13.9% with a relative error of 8.19%.