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Background: Hypertension-induced cardiac dysfunction is variable among different anti-hypertensive medications. This study compares the effects of telmisartan and enalapril on echocardiographic parameters in hypertensive patients., Materials and Methods: This was a randomised single blinded study. Eighty hypertensive patients were included in this study and they were randomly allocated into two study groups: Group 1 included 40 patients who took telmisartan 80mg once daily for six months. Group 2 included 40 patients who took enalapril, 20mg once daily for six months. An additional 40 healthy participants were enrolled in the study as controls (Group 3). Baseline echocardiographic scan was done at the start of the study and after 6 months of treatment including assessment of left ventricular systolic and diastolic functions with assessment of left ventricular mass index, in addition to measurements of blood pressure, heart rate and double product., Results: Both group 1 and group 2 (telmisartan and enalapril groups respectively) showed comparable statistically significant improvement in the diastolic functional parameters (P<0.010), while both medications didn't demonstrate changes in the systolic functional parameters. Furthermore, telmisartan was significantly effective in reducing the interventricular septal thickness and left ventricular mass index (P<0.010)., Conclusions: Both drugs interfere with renin-angiotensin aldosterone system, protecting the myocardium from high blood pressure. Findings from our study provide key results for physicians in deciding the appropriate antihypertensive drug for each patient depending based on the patient's intolerability for either medication., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Dendritic cells (DCs) are critical for the initiation of immune responses including activation of CD8 T cells. Intracellular reactive oxygen species (ROS) levels influence DC maturation and function. Intracellular heme, a product of catabolism of heme-containing metalloproteins, is a key inducer of ROS. Intracellular heme levels are regulated by heme oxygenase-1 (HO-1), which catalyzes the degradation of heme. Heme oxygenase-1 has been implicated in regulating DC maturation; however, its role in other DC functions is unclear. Furthermore, the signaling pathways modulated by HO-1 in DCs are unknown. In this study, we demonstrate that inhibition of HO-1 activity in murine bone marrow-derived immature DCs (iDCs) resulted in DCs with raised intracellular ROS levels, a mature phenotype, impaired phagocytic and endocytic function, and increased capacity to stimulate antigen-specific CD8 T cells. Interestingly, our results reveal that the increased ROS levels following HO-1 inhibition did not underlie the changes in phenotype and functions observed in these iDCs. Importantly, we show that the p38 mitogen-activated protein kinase (p38 MAPK), cAMP-responsive element binding protein (CREB), and activating transcription factor 1 (ATF1) pathway is involved in the mediation of the phenotypic and functional changes arising from HO-1 inhibition. Furthermore, up-regulation of HO-1 activity rendered iDCs refractory to lipopolysaccharide-induced activation of p38 MAPK-CREB/ATF1 pathway and DC maturation. Finally, we demonstrate that treatment of iDC with the HO-1 substrate, heme, recapitulates the effects that result from HO-1 inhibition. Based on these results, we conclude that HO-1 regulates DC maturation and function by modulating the p38 MAPK-CREB/ATF1 signaling axis., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Nrf2 is a redox-responsive transcription factor that has been implicated in the regulation of DC immune function. Loss of Nrf2 results in increased co-stimulatory molecule expression, enhanced T cell stimulatory capacity, and increased reactive oxygen species (ROS) levels in murine immature DCs (iDCs). It is unknown whether altered immune function of Nrf2-deficient DCs (Nrf2(-/-) iDCs) is due to elevated ROS levels. Furthermore, it is unclear which intracellular signaling pathways are involved in Nrf2-mediated regulation of DC function. Using antioxidant vitamins to reset ROS levels in Nrf2(-/-) iDCs, we show that elevated ROS is not responsible for the altered phenotype and function of these DCs. Pharmacological inhibitors were used to explore the role of key MAPKs in mediating the altered phenotype and function in Nrf2(-/-) iDCs. We demonstrate that the increased co-stimulatory molecule expression (MHC II and CD86) and antigen-specific T cell activation capacity observed in Nrf2(-/-) iDCs was reversed by inhibition of p38 MAPK but not JNK. Importantly, we provide evidence for increased phosphorylation of cAMP-responsive element binding protein (CREB) and activating transcription factor 1 (ATF1), transcription factors that are downstream of p38 MAPK. The increased phosphorylation of CREB/ATF1 in Nrf2(-/-) iDCs was sensitive to p38 MAPK inhibition. We also show data to implicate heme oxygenase-1 as a potential molecular link between Nrf2 and CREB/ATF1. These results indicate that dysregulation of p38 MAPK-CREB/ATF1 signaling axis underlies the altered function and phenotype in Nrf2-deficient DCs. Our findings provide new insights into the mechanisms by which Nrf2 mediates regulation of DC function.