The present study was performed to evaluate the role of an interaction between the endothelin (ET) and the renin-angiotensin systems (RAS) in the development and maintenance of hypertension and in hypertension-associated end-organ damage in heterozygous male and female transgenic rats harboring the mouse Ren-2 renin gene (TGR). Twenty-eight days old heterozygous TGR and age-matched transgene-negative normotensive Hannover Sprague-Dawley rats (HanSD) were randomly assigned to groups with normal-salt (NS) or high-salt (HS) intake. Nonselective ETA/ETB receptor blockade was achieved with bosentan (100 mg.kg-1.day-1). All male and female HanSD as well as heterozygous TGR on NS exhibited 100 % survival rate until 180 days of age (end of experiment). HS diet in heterozygous TGR induced a transition from benign to malignant phase hypertension. The survival rates in male and in female heterozygous TGR on the HS diet were 46 % and 80 %, respectively, and were significantly improved by administration of bosentan to 76 % and 97 %, respectively. Treatment with bosentan did not influence either the course of hypertension (measured by plethysmography in conscious animals) or the final levels of blood pressure (measured by a direct method in anesthetized rats) in any of the experimental groups of HanSD or TGR. Administration of bosentan in heterozygous TGR fed the HS diet markedly reduced proteinuria, glomerulosclerosis and attenuated the development of cardiac hypertrophy compared with untreated TGR. Our data show that the ET receptor blockade markedly improves the survival rate and ameliorates end-organ damage in heterozygous TGR exposed to HS diet. These findings indicate that the interaction between the RAS and ET systems plays an important role in the development of hypertension-associated end-organ damage in TGR exposed to salt-loading.
Cardiovascular disease is a major cause of morbidity and mortality in young adults with end-stage renal disease (ESRD), but its basis is still not well understood. We therefore evaluated the determinants of atherosclerosis in children with ESRD. A total of 37 children with ESRD (with 31 who had undergone transplantation) were examined and compared to a control group comprising 22 healthy children. The common carotid intimamedia thickness (CIMT) was measured by ultrasound as a marker of preclinical atherosclerosis. The association of CIMT with anthropometrical data, blood pressure, plasma lipid levels, and other biochemical parameters potentially related to cardiovascular disease was evaluated. Children with ESRD had significantly higher CIMT, blood pressure, and levels of lipoprotein (a), urea, creatinine, ferritin, homocysteine, and serum uric acid as well as significantly lower values of apolipoprotein A. The atherogenic index of plasma (log(triglycerides/HDL cholesterol)) was also higher in patients with ESRD; however, this difference reached only borderline significance. In addition, a negative correlation was found between CIMT and serum albumin and bilirubin in the ESRD group, and this correlation was independent of age and body mass index. In the control group, a significant positive correlation was observed between CIMT and ferritin levels. Factors other than traditional cardiovascular properties, such as the antioxidative capacity of circulating blood, may be of importance during the early stages of atherosclerosis in children with endstage renal disease., H. M. Dvořáková ... [et al.]., and Obsahuje seznam literatury
It is believed that atherogenesis is a multifactorial process, which could already start in utero. Development of atherosclerosis progresses over decades and leads to the cardiovascular morbidity and mortality in adulthood. At present, we have no exact explanation for all the risk factors acting in the pathogenesis of atherosclerosis. This review should provide an overview about the possible role of intrauterine undernutrition in the development of risk factors for cardiovascular disease. Intrauterine undernutrition leads to changes in fetal growth and metabolism and programs later development of some of these risk factors. A number of experimental and human studies indicates that hypertension as well as impaired cholesterol and glucose metabolism are affected by intrauterine growth. Intrauterine undernutrition plays an important role and acts synergistically with numerous genetic and environmental factors in the development of atherosclerosis. There is evidence that undernutrition of the fetus has permanent effects on the health status of human individuals., P. Szitányi, J. Janda, R. Poledne., and Obsahuje bibliografii