Potassium channels mediate nitric oxide-induced vasorelaxation in arteries supplying colon cancer.

Prostaglandins Other Lipid Mediat

Department of Biology, College of Science, University of Zakho, Duhok, Kurdistan Region, Iraq; Department of Biology, College of Science, University of Nawroz, Duhok, Kurdistan Region, Iraq.

Published: December 2024

Introduction: Aberrant vascular function and cancer growth are closely related, with nitric oxide (NO) being a key factor in vascular tone regulation. This study provides Novel insights into the distinctive mechanisms underlying cancer-associated vascular dysfunction by investigating the involvement of potassium (K) channels in NO-mediated vasorelaxation within arteries supplying colon cancer.

Methods: Arterial segments from colon cancer patients were isolated and sectioned into rings, these rings were mounted in an organ bath filled with Krebs' solution and maintained at 37°C. Isometric tension recordings were obtained using a force transducer connected to a PowerLab Data Acquisition System. Arterial segments were pre-incubated with a variety of K channel blockers, both individually and in combination, including glibenclamide (GLIB), barium chloride (BaCl), tetraethylammonium (TEA), and 4-aminopyridine (4-AP). Concentration-response curves were designed to evaluate how K channel blocking affected the vasodilation caused by NO.

Results: Sodium nitroprusside (SNP) induced vasorelaxation in arterial rings from colon cancer, influenced by specific K+ channels. Pre-incubation with TEA significantly reduced Emax to 60.22 ± 8.14 %, compared to 124.91 ± 15.07 % in controls, while GLIB decreased Emax to 113.10 ± 3.87 %. BaCl2 and 4-AP further diminished relaxation, and combined K channel blockers showed complex, non-additive effects. Distinct contributions of K and K channels to NO-induced vasodilation were elucidated. Additionally, interaction between NO and L-type calcium (Ca) channels suggested a novel vasorelaxation mechanism in cancerous tissues.

Conclusion: This research offers new perspectives on the intricate relationship between vascular biology and cancer development, emphasizing the promise of targeting potassium channels to address vascular abnormalities in cancer.

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Source
http://dx.doi.org/10.1016/j.prostaglandins.2024.106937DOI Listing

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