Excitement always greets the development of a new class of therapeutic drug, representing as it does the combined efforts of the pharmaceutical industry, research laboratories and clinicians. Endothelin (ET)-receptor antagonists are being actively developed as new therapeutic agents for cardiovascular diseases, and may also be of use in other pathological conditions. Based on early and indirect evidence, ET has been implicated in the pathophysiology of hypertension; the receptor antagonists have been studied quite extensively in this setting at the preclinical level. We now possess direct evidence that such drugs are effective as antihypertensives in some experimental models of hypertension. Furthermore, the ability of ET-receptor antagonists to prevent hypertension-induced end-organ damage is also well documented. Their capacity to reverse already established target organ alterations remains poorly defined. Based on our current preclinical and clinical knowledge, this review presents the anticipated clinical usefulness of these new drugs, both in terms of blood pressure reduction and the protection of target organs.
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http://dx.doi.org/10.1517/13543784.8.11.1807 | DOI Listing |
Front Pharmacol
December 2024
Systems Pharmacology and Translational Therapeutics Laboratory, The Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University, Chieti, Italy.
Inflammation plays a critical role in the pathogenesis of various diseases by promoting the acquisition of new functional traits by different cell types. Shared risk factors between cardiovascular disease and cancer, including smoking, obesity, diabetes, high-fat diet, low physical activity, and alcohol consumption, contribute to inflammation linked to platelet activation. Platelets contribute to an inflammatory state by activating various normal cells, such as fibroblasts, immune cells, and vascular cells.
View Article and Find Full Text PDFCan J Kidney Health Dis
January 2025
Division of Nephrology, Department of Medicine, Ottawa Hospital, University of Ottawa, ON, Canada.
Background: Patients with end-stage kidney disease (ESKD) have high rates of gastrointestinal bleeding due to several risk factors including platelet dysfunction, comorbid illness, and use of antiplatelet medications. Proton pump inhibitors (PPIs) reduce gastrointestinal bleeding and are recommended for high-risk patients such as those prescribed dual antiplatelet therapy (DAPT). Whether inappropriate duration of DAPT therapy and/or lack of appropriate PPI use contribute to the known elevated risk of gastrointestinal bleeding in hemodialysis patients is not known.
View Article and Find Full Text PDFFront Chem
December 2024
Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, Oujda, Morocco.
Ethnopharmacological Relevance: In Moroccan traditional medicine, plants from the Apiaceae family are widely utilized in folk medicine to treat various diseases associated with the digestive system. plays an important role as an antispasmodic that has been traditionally used, especially to treat digestive tract diseases in children.
Aim Of The Study: The aim of this research was to verify the traditional use by assessing the relaxant and spasmolytic activities of essential oil (ALEO) and then comparing them to the effects and potency of the major constituent of ALEO, which is perillaldehyde.
The endogenous dynorphin/kappa opioid receptor (KOR) system in the brain mediates the dysphoric effects of stress, and KOR antagonists may have therapeutic potential for the treatment of drug addiction, depression, and psychosis. One class of KOR antagonists, the long-acting norBNI-like antagonists, have been suggested to act by causing KOR inactivation through a cJun-kinase mechanism rather than by competitive inhibition. In this study, we screened for other opioid ligands that might produce norBNI-like KOR inactivation and found that nalfurafine (a G-biased KOR agonist) and nalmefene (a KOR partial agonist) also produce long-lasting KOR inactivation.
View Article and Find Full Text PDFTruncated TrkB (TrkBT1), traditionally considered a dominant-negative regulator of full-length TrkB (TrkBTK+), remains poorly understood in peripheral sensory neurons, particularly nociceptors. Furthermore, sensory neuronal TrkB expression and function has been traditionally associated with non-nociceptive neurons, particularly Aδ low-threshold mechanoreceptors. This study challenges prevailing assumptions by demonstrating that TrkBT1 is the predominant TrkB isoform expressed in sensory neurons and plays a functional role in modulating neuronal activity.
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