The relationship between angiotensin II (ANG II) and endothelin-1 (ET-1) is known to be complex; both peptides can initiate and potentiate the gene expression of each other. This pilot study investigated the effects of the AT1 receptor blocker losartan or the direct renin inhibitor aliskiren on mean arterial pressure (MAP) and albuminuria and the renal ANG II and ET-1 levels. 3-month-old male Ren-2 transgenic rats (TGR) were treated either with losartan (5 mg kg-1 day-1) or aliskiren (10 mg kg-1 day-1) for 10 weeks. At the end of the experiment, rats were decapitated and cortical and papillary parts of kidneys were separated. Plasma and tissue ANG II levels were measured by RIA and tissue ET-1 concentrations by ELISA. In all four groups of animals ET-1 levels were lowest in renal cortex and more than 100-fold higher in the papilla. Cortical and papillary ET-1 concentrations in untreated TGR significantly exceeded those of control HanSD rats and were significantly depressed by both drugs. In both strains, papillary ANG II concentrations were moderately but significantly higher than cortical ANG II, TGR exhibited higher ANG II levels both in cortex and papilla as compared to control HanSD rats. Aliskiren and losartan at the doses used depressed similarly the levels of ANG II in cortex and papilla and reduced ET-1 significantly in the renal cortex and papilla below control levels in HanSD rats. Albuminuria, which was more than twice as high in TGR as in HanSD rats, was normalized with aliskiren and reduced by 28 % with losartan, although MAP was reduced to a similar degree by both drugs. Despite similar reductions of MAP and renal ET-1 and ANG II levels aliskiren appears to be more effective than losartan, at the doses used, in reducing albuminuria in heterozygous hypertensive Ren-2 rats., Z. Vaňourková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
1a_Caveolin-1 (CAV-1) is the main structural component of caveolae, acting as a modulator of signal transduction. CAV-1 might be involved in the pathophysiology of microvascular complications in Type 1 diabetes (DM). We sought to determine whether fractionation on sucrose gradient (SF), a method routinely utilized for isolation of caveolar fractions in homogenous cell lines, is applicable for CAV-1-related studies in tissues with multiple cell types, such as the normal rat kidney cortex (C). Using this method, we also determined whether streptozotocin- induced DM in rats (4-week duration) leads to changes in renal subcellular targeting of CAV-1, and evaluated the effects of tight metabolic control (insulin, 12 IU /day) and angiotensin receptor blocker, losartan (4 weeks, 20 mg/kg/day). Immunoblotting of individual fractions obtained from C revealed CAV-1 expression in fractions 4-6 that corresponded to light scattering band that typically forms after separating cellular fractions on SF. These fractions were considered to be caveolar fractions. In C, CAV-1 was also detectable in fracti ons 8-10. These and all other fractions except caveolar fractions were considered to be non-caveolar fractions. A ratio of caveolar/non-caveolar expression of CAV-1 (CNCR) was computed for each renal cortex allowing comparisons of CAV-1 subcellular distribution in C and DM rats, and effects of treatments., 2a_Using this approach, DM was characterized by marked increases in CNCR as compared to C (5.54±1.56 vs. 2.65±1.33, p<0. 05) that were reduced by treatment with insulin (0.78±0. 24, p<0.01 vs. DM) or losartan (0.84±0.06, p<0.01 vs. DM). In summary, analysis of CAV-1 following the SF of renal cortex detected similar distribution of the protein as in homogenous cell lines, DM-induced changes in CAV-1 targeting, and the effects of pharmacological treatments. This suggests applicability of SF in studies focusing on CAV-1 targeting in organs with various cell lines in vivo., H. Demová, R. Komers., and Obsahuje seznam literatury
We studied the effect of losartan on baroreflex sensitivity (BRS) and heart rate variability (HRV) of adult Wistar rats during acute and chronic inhibition of nitric oxide synthesis by NG -nitro-Larginine methyl ester (L-NAME). Chronic L-NAME administration (50 mg/kg per day for 7 days, orally through gavage) increased mean arterial pressure (MAP), heart rate but significantly decreased BRS. In addition, a significant fall of standard deviation of normal RR intervals, total spectral power, high frequency spectral power and a rise of low frequency to high frequency (LF: HF) ratio was seen. Acute L-NAME administration (30 mg/kg, i.v. bolus dose) also raised MAP and impaired HRV but it was associated with augmented BRS for bradycardia reflex. Losartan treatment (10 mg/kg, i.v.) in both acute and chronic L-NAME treated rats, decreased MAP but the difference was not significant. On the other hand, losartan administration normalized depressed BRS for bradycardia reflex and significantly reduced LF to HF ratio in chronic L-NAME treated rats. But this improvement was not observed in acute L-NAME group. These results indicate importance of mechanisms other than renin-angiotensin system in the pressor response of both acute as well as chronic L-NAME. However, autonomic dysregulation especially following chronic L-NAME appears to be partly angiotensin dependent., M. Chaswal ... [et al.]., and Obsahuje seznam literatury
No data are available about the effects of AT1 receptor antagonist losartan on the skeleton and there is also little information on the activity of an ACE inhibitor enalapril on bone metabolism. It is widely believed that the vasculature plays an important role in bone remodeling under normal and pathological conditions. We treated 14-week-old female Wistar rats with losartan, enalapril or saline. Administration of the ACE inhibitor enalapril and angiotensin II antagonist losartan had no effect on total malondialdehyde (MDA) in the blood and on urinary excretion of some eicosanoids and their metabolites. The administration of enalapril and losartan in a dose recommended for the treatment of hypertension did not cause significant changes in bone density, the ash and mineral content or morphometric parameters of the femur compared to the values found in control female rats., P. D. Broulík, V. Tesař, T. Zima, M. Jirsa., and Obsahuje bibliografii
Alterations in geometry and structure of coronary arteries have marked consequences on blood flow to the respective area. We evaluated long-term effect of losartan on blood pressure (BP), heart weight/body weight (HW/BW), geometry and structure of septal branch of coronary artery (RS) of young SHR and Wistar rats. Four-week-old Wistar rats and SHR were used. Losartan was administered (20 mg/kg/day) in drinking water by gavage for 5 weeks. BP was measured by plethysmographic method. Cardiovascular system was perfused with a fixative (120 mm Hg). RS was processed for electron microscopy. Wall thickness of intima + media (WT), inner diameter (ID), cross-sectional area of intima + media (CSA), volume dens ities (VD) of endothelial cells (EC), extracellular matrix (ECM) of intima, smooth muscle cells (SMC) and ECM of media were eval uated. BP of 4-week-old SHR did not differ from that of Wistar rats. BP, HW/BW, WT, CSA, WT/ID, CSAs of SMC, ECM of media were increased in 9-week- old SHR, whereas their VD and CSA of EC were decreased. Losartan administration decreased BP and HW/BW in both groups. Geometry of RS was affected only in SHR (reduction of WT, CSA, WT/ID and increased of ID, circumferential tension, VD and CSA of EC). Losartan administration reduced BP and myocardial mass in both groups and beneficially affected geometry and structure of coronary artery in SHR., R. Koprdová, M. Cebová, F. Kristek., and Obsahuje seznam literatury