This study analyzes the role of angiotensin II (Ang II), via AT1) receptors, in the involvement of cyclooxygenase (COX)-2-derived prostanoids in phenylephrine responses in normotensive rats (Wistar Kyoto; WKY) and spontaneously hypertensive rats (SHR). Aorta from rats untreated or treated for 12 weeks with losartan (15 mg/kg . day) or hydralazine plus hydrochlorothiazide (44 and 9.4 mg/kg . day, respectively) and vascular smooth muscle cells (VSMC) from SHR were used. Vascular reactivity was analyzed by isometric recording; COX-2 expression by Western blot and reverse transcription-polymerase chain reaction; prostaglandin (PG)I2, PGF(2alpha), 8-isoprostane, and total antioxidant status (TAS) by commercial kits; superoxide anion (O2*-) by lucigenin chemiluminescence; and plasmatic malondialdehyde (MDA) by thiobarbituric acid assay. The COX-2 inhibitor N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methane sulfonamide (NS-398) at 1 microM reduced phenylephrine responses more in SHR than in WKY rats. COX-2 protein and mRNA expressions, PGF(2alpha), PGI2, 8-isoprostane, and O2*- production, and MDA levels were higher in SHR, but TAS was similar in both strains. Losartan, but not hydralazine-hydrochlorothiazide treatment, reduced COX-2 expression and the effect of NS-398 on phenylephrine responses in SHR. Losartan also increased TAS and reduced PGF(2alpha), PGI2, 8-isoprostane, and O2*- production and MDA levels in SHR. Ang II (0.1 microM) induced COX-2 expression in VSMC from SHR that was reduced by 30 microM apocynin and 100 microM allopurinol, NADPH oxidase, and xanthine oxidase inhibitors, respectively. In conclusion, AT1 receptor activation by Ang II could be involved in the increased participation of COX-2-derived contractile prostanoids in vasoconstriction to phenylephrine with hypertension, probably through COX-2 expression regulation. The increased oxidative stress seems to be one of the mechanisms involved.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1124/jpet.106.115287 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pterostilbene protects against lipopolysaccharide-induced inflammation and blood-brain barrier disruption in immortalized brain endothelial cell lines in vitro.
Sci Rep
January 2025
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.
Brain microvascular endothelial cells are connected by tight junction (TJ) proteins and interacted by adhesion molecules, which participate in the selective permeability of the blood-brain barrier (BBB). The disruption of BBB is associated with the progression of cerebral diseases. Pterostilbene is a natural compound found in blueberries and grapes with a wide range of biological activities, including anti-inflammatory, antioxidant, and anti-diabetic effects.
View Article and Find Full Text PDFCardioprotective potential of tectochrysin against vanadium induced heart damage via regulating NLRP3, JAK1/STAT3 and NF-κB pathway.
J Trace Elem Med Biol
January 2025
Department of Pathology, College of Medicine, King Khalid University, Asir 61421, Saudi Arabia; Department of Forensic Medicine and Clinical Toxicology, Mansoura University, Egypt.
Background: Vanadium (VAN) is a significant trace element, but its higher exposure is reported to cause severe organ toxicity. Tectochrysin (TEC) is a naturally derived flavonoid which demonstrates a wide range of pharmacological properties.
Aim: The current study was planned to assess the cardioprotective potential of TEC against VAN induced cardiotoxicity in rats via regulating biochemical, and histological profile.
Modulation of PI3K/AKT signaling and DFT modeling via selected pharmaceutical compounds attenuates carrageenan-induced inflammation and oxidative stress in rats.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, 12622, Egypt.
The main goal of the current study is to estimate the in vivo anti-inflammatory/antioxidant ability of four selected pharmaceutical compounds: bisoprolol (Biso), piracetam (Pirc), clopidogrel (Clop), and cinnarizine (Cinna). Indomethacin (Indo) was used as a reference drug to perform a realistic comparison between the four compounds and the Indo in vivo through tracking PI3K/AKT signaling and computational chemistry via density functional theory (DFT) modeling to analyze the electrostatic potential across the molecule and provide insight into the regions for receptor binding of the studied compounds. To achieve the safe dose of these compounds, cytotoxicity was performed against isolated adipose tissue-derived mesenchymal stem cells (ADMSCs) using MTT assay.
View Article and Find Full Text PDFBiomimetic Fe3O4 Nanozymes Promote Apoptosis in Breast Cancer Cell Lines via Free Radical Scavenging and Inhibition of RelA/p65.
Curr Pharm Biotechnol
January 2025
Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, China.
Introduction: Iron oxide nanozyme was synthesized from the fruit peel extract of pomegranate, which served as a reducing agent during the green synthesis. The scavenging of reactive oxygen species is often accompanied by immunomodulation following antiproliferative effects due to the crosstalk between the proteins involved in the inter-related signaling pathways.
Method: In the current study, the green synthesized nanozyme was studied for its ability to induce apoptosis in breast cancer cell lines.
The COX-2 Inhibitor Celecoxib Sensitizes Nasopharyngeal Carcinoma Cells to Ferroptosis.
Curr Cancer Drug Targets
January 2025
Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
Background: Nasopharyngeal cancer (NPC) is prevalent in Southeast Asia and North Africa, which is generally associated with limited treatment options and poor patient prognosis.
Objective: Ferroptosis is a recently observed cell death modality and has been shown to link to the efficacy of different anti-cancer treatments, thus offering opportunities to the development of novel therapies. This study aims to investigate the potentiating effects of COX-2 inhibitors on ferroptosis in nasopharyngeal cancer.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!