Hypertension contributes greatly to global disease burden and in many patients current treatments do not adequately control blood pressure (BP). Endothelin-1 (ET-1) is a potent vasoconstrictor that is implicated in the pathogenesis of hypertension, including the hypertension that is often associated with chronic kidney disease (CKD) and the metabolic syndrome. ET receptor antagonists, currently licensed for the treatment of pulmonary arterial hypertension and scleroderma-related digital ulcers, are being investigated for the treatment of hypertension. Clinical trials have addressed the use of ET receptor antagonists as monotherapy in primary hypertension, as an add-on therapy in resistant hypertension and in CKD. This review will evaluate the current evidence regarding the therapeutic potential of ET receptor antagonists in hypertension, as well as highlighting important issues that still need to be addressed.
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http://dx.doi.org/10.1007/s11906-013-0380-1 | DOI Listing |
ACS Chem Neurosci
January 2025
Departments of Psychiatry and Neurology, Division of Molecular Therapeutics, New York State Psychiatric Institute, Columbia University Medical Center, New York, New York 10032, United States.
Voluntary movement, motivation, and reinforcement learning depend on the activity of ventral midbrain neurons, which extend axons to release dopamine (DA) in the striatum. These neurons exhibit two patterns of action potential activity: low-frequency tonic activity that is intrinsically generated and superimposed high-frequency phasic bursts that are driven by synaptic inputs. acute striatal brain preparations are widely employed to study the regulation of evoked DA release but exhibit very different DA release kinetics than recordings.
View Article and Find Full Text PDFBr J Pharmacol
January 2025
Center for Clinical Pharmacology, Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Background And Purpose: Pituitary adenylate cyclase activating polypeptide (PACAP) is a human migraine trigger that is being targeted for migraine. The δ-opioid receptor (δ-receptor) is a novel target for the treatment of migraine, but its mechanism remains unclear. The goals of this study were to develop a mouse PACAP-headache model using clinically significant doses of PACAP; determine the effects of δ-receptor activation in this model; and investigate the co-expression of δ-receptors, PACAP and PACAP-PAC1 receptor.
View Article and Find Full Text PDFJ Clin Med
January 2025
Corewell Health, Grand Rapids, MI 49503, USA.
Chronic cough is a distressing and prevalent symptom in interstitial lung disease (ILD), significantly impairing quality of life (QoL) and contributing to disease progression, particularly in idiopathic pulmonary fibrosis (IPF). It is associated with physical discomfort, psychological distress, and social isolation and is often refractory to conventional therapies. The pathophysiology of cough in ILD is complex and multifactorial, involving neural hypersensitivity, structural lung changes, inflammatory processes, and comorbid conditions such as gastroesophageal reflux disease (GERD).
View Article and Find Full Text PDFNutrients
December 2024
Department of Nephrocardiology, Medical University of Lodz, 90-549 Lodz, Poland.
This narrative review explores the benefits and risks of cannabinoids in kidney health, particularly in individuals with pre-existing renal conditions. It discusses the roles of cannabinoid receptor ligands (phytocannabinoids, synthetic cannabinoids, and endocannabinoids) in kidney physiology. The metabolism and excretion of these substances are also highlighted, with partial elimination occurring via the kidneys.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
G protein-coupled receptors (GPCRs) play essential roles in numerous physiological processes and are key targets for drug development. Among them, adhesion GPCRs (aGPCRs) stand out for their unique domain structures and diverse functions. ADGRG2 is a member of the aGPCR family and is involved in the regulation of various systems in the human body, including reproductive, nervous, cardiovascular, and endocrine systems.
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