Władysław Teodor Benda

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Thrombin inhibition prevents endothelial dysfunction and reverses 20-HETE overproduction without affecting blood pressure in angiotensin II-induced hypertension in mice

Angiotensin II (Ang II) induces hypertension and endothelial dysfunction, but the involvement of thrombin in these responses is not clear. Here, we assessed the effects of the inhibition of thrombin activity by dabigatran on Ang II-induced hypertension and endothelial dysfunction in mice with a particular focus on NO- and 20-HETE-dependent pathways. As expected, dabigatran administration significantly delayed thrombin generation (CAT assay) in Ang II-treated hypertensive mice, and interestingly, it prevented endothelial dysfunction development, but it did not affect elevated blood pressure nor excessive aortic wall thickening. Dabigatran’s effects on endothelial function in Ang II-treated mice were evidenced by improved NO-dependent relaxation in the aorta in response to acetylcholine in vivo (MRI measurements) and increased systemic NO bioavailability (NO2− quantification) with a concomitant increased ex vivo production of endothelium-derived NO (EPR analysis). Dabigatran treatment also contributed to the reduction in the endothelial expression of pro-inflammatory vWF and ICAM-1. Interestingly, the fall in systemic NO bioavailability in Ang II-treated mice was associated with increased 20-HETE concentration in plasma (UPLC-MS/MS analysis), which was normalised by dabigatran treatment. Taking together, the inhibition of thrombin activity in Ang II-induced hypertension in mice improves the NO-dependent function of vascular endothelium and normalises the 20-HETE-depedent pathway without affecting the blood pressure and vascular remodelling

Greenhouse gas mitigation on croplands: clarifying the debate on knowns, unknowns and risks to move forward with effective management interventions

The opportunity of agricultural management practices to sequester soil organic carbon (SOC) is recognized as an important strategy for mitigating climate change. However, there is low confidence when it comes to understanding the magnitude of the climate benefit we can expect from SOC sequestration or how best to achieve it. Several issues are often confounded when it comes to the mitigation potential of SOC sequestration and greenhouse gas (GHG) reductions from agriculture, creating confusion and making it difficult to clearly identify the knowns, unknowns and risks to implementing policy and practice recommendations. Here, we identify and explain four major areas of uncertainty: (1) the expected changes in soil carbon or GHG emissions resulting from agricultural management practice changes; (2) the extent to which social, environmental and economic factors constrain mitigation potential; (3) the ability to execute reliable measurement, monitoring, reporting and verification (MMRV) frameworks; and (4) the perception of risk associated with different ways of promoting practice adoption (e.g., voluntary carbon markets fueled by the private sector, pay-for-practice programs funded by public investment). We aim to pinpoint knowledge gaps and areas of disagreement to help right-size expectations and guide effective investment in GHG removals and reductions from agriculture