engleski

Assessment of the role of ion channels in flow- induced dilation mechanisms of a carotid artery in low salt and high salt fed Tff3−/−/C57BL/6N mice and their wild type controls

Introduction: This study aimed to assess the role of ion channels in flow-induced dilation (FID) in isolated carotid arteries of Tff3-/- knockout mice and C57BL/6N mice (wild type controls) on low (LS) and high salt (HS) diet. Methods: Male, ten-weeks-old transgenic Tff3−/ −/C57BL/6N (Tff3−/−) knockout mice and WT/C57BL/6N (WT) (parental strain) healthy mice were divided in LS (0.4% NaCl in rodent chow) and HS (4% NaCl in rodent chow fed for 1 week) groups. After anaesthesia, mice were decapitated and carotid arteries were isolated and pressurized for 60’at 100 mmHg to assess basal diameter and then subjected to flow at pressure gradients Δ100-Δ180 mmHg. FID was determined in the presence of antagonists of large conductance Ca2+-activated K+-channel (iberiotoxin), ATP- sensitive potassium channels (glibenclamide) and TRPV4 (RN-1734). Data were analysed using Two-way ANOVA tests ; p<0.05 was considered significant. Results: FID was similar between the Tff3−/−_LS and Tff3−/−_HS groups, while FID was reduced in WT_ HS mice compared to the WT_LS group. FID was also reduced in Tff3−/−_LS compared to WT_LS mice. In the Tff3-/-_ LS group, iberiotoxin and glibenclamide reduced FID at ∆180 mm Hg, while had no effect in the Tff3-/-_HS group. In the WT_LS group all inhibitors reduced FID at ∆140- 180 mm Hg while had no effect in the WT_HS. Discussion: HS diet causes impaired responses to FID in WT mice but not in Tff3−/− mice. In Tff3−/ − mice on LS diet Ca2+-activated K+- channel and ATP- sensitive potassium channels have a significant role in FID. In WT_ mice on LS diet, beside Ca2+-activated K+- channel and ATP- sensitive potassium channels, TRPV4 contributes to FID. In Tff3−/− and WT mice on HS diet, applied antagonists have no effect on FID. Conclusion: Genetic modification as well as dietary intake significantly affect the mechanisms of FID by altering the ion channels' engagement. Funding and financial support: This study was supported by the Croatian Science Foundation under the project IP-2014-09-6380 (V-ELI Athero), VIF-2018-MEFOS-09-1509 grant and Faculty of Medicine Osijek Institutional grant #IP-1- MEFOS2019 and #IP-1-MEFOS2020 (2019, 2020 ; PI Ines Drenjančević). Ethical Committee: All experimental procedures conformed to the European Guidelines for the Care and Use of Laboratory Animals (Directive 86/609) and were approved by the local and national Ethical Committee (No. 2158/61-02-139/2-06 and No. 2158/61-07-14-119). Acknowledgements: Thank to Cedars - Sinai Medical Center’s International Research and Innovation in Medicine Program, the Association for Regional Cooperation in the Fields of Health, Science and Technology (RECOOP HST Association) for their support of our organization as participating Cedars – Sinai Medical Center - RECOOP Research Centers (CRRC). Session: cardiovascular diseases (CVD)

Tff3 gene, high salt diet, ion channels, artery, flow-induced dilation

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