Nitric oxide (NO) generated by endothelial cells to relax vascular smooth muscle is one of the most intensely studied molecules in the past 25 years. Much of what is known about NO regulation of NO is based on blockade of its generation and analysis of changes in vascular regulation. This approach has been useful to demonstrate the importance of NO in large scale forms of regulation but provides less information on the nuances of NO regulation. However, there is a growing body of studies on multiple types of in vivo measurement of NO in normal and pathological conditions. This discussion will focus on in vivo studies and how they are reshaping the understanding of NO's role in vascular resistance regulation and the pathologies of hypertension and diabetes mellitus. The role of microelectrode measurements in the measurement of [NO] will be considered because much of the controversy about what NO does and at what concentration depends upon the measurement methodology. For those studies where the technology has been tested and found to be well founded, the concept evolving is that the stresses imposed on the vasculature in the form of flow-mediated stimulation, chemicals within the tissue, and oxygen tension can cause rapid and large changes in the NO concentration to affect vascular regulation. All these functions are compromised in both animal and human forms of hypertension and diabetes mellitus due to altered regulation of endothelial cells and formation of oxidants that both damage endothelial cells and change the regulation of endothelial nitric oxide synthase.
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http://dx.doi.org/10.1002/cphy.c140052 | DOI Listing |
Theranostics
January 2025
Department of neurology, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea.
It remains unclear why unilateral proximal carotid artery occlusion (UCAO) causes benign oligemia in mice, yet leads to various outcomes (asymptomatic-to-death) in humans. We hypothesized that inhibition of nitric oxide synthase (NOS) both transforms UCAO-mediated oligemia into full infarction and expands pre-existing infarction. Using 900 mice, we i) investigated stroke-related effects of UCAO with/without intraperitoneal administration of the NOS inhibitor (NOSi) N-nitro-L-arginine methyl ester (L-NAME, 400 mg/kg); ii) examined the rescue effect of the NO-donor, molsidomine (200 mg/kg at 30 minutes); and iii) tested the impact of antiplatelet medications.
View Article and Find Full Text PDFJ Cancer
January 2025
Department of Laboratory Medicine, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People's Republic of China.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. However, the molecular mechanism underlying the occurrence and development of HCC remains unclear. We are interested in the function of m6A methylation enzyme WTAP in the occurrence and development of HCC.
View Article and Find Full Text PDFJ Res Med Sci
October 2024
Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah, Saudi Arabia.
Background: Evidence-based screening is crucial to detect myocardial ischemia in high-risk diabetics. We explored the relationship between nitric oxide (NO) levels, lipid profile indices, and atherogenic index of plasma (AIP) in type 2 diabetics with coronary artery disease (CAD) and to determine their potential as prognostic markers.
Materials And Methods: A case-control study included 50 diabetics with CAD (cases), 30 diabetics without CAD (control 1), and 23 healthy controls (control 2).
Future Med Chem
January 2025
Isra College of Pharmacy, Isra University, Hyderabad, Pakistan.
Aim: To evaluate the anti-inflammatory potential of novel class of chemical compounds designed by the linkage of carbothioamide moiety with pyridine.
Materials & Methods: In silico analysis was conducted using molecular docking followed by an in vitro cytotoxicity assay and evaluation of anti-inflammatory activity. Subsequently, in vivo performance was determined using the Complete Freund's Adjuvant-induced inflammatory model, employing macroscopic, histopathological, and protein expression analyses.
Nature
January 2025
Columbia Center for Translational Immunology, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
Stem cells reside in specialized microenvironments, termed niches, at several different locations in tissues. The differential functions of heterogeneous stem cells and niches are important given the increasing clinical applications of stem-cell transplantation and immunotherapy. Whether hierarchical structures among stem cells at distinct niches exist and further control aspects of immune tolerance is unknown.
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