engleski

Assessment of the effect of carnosine supplementation on flow induced dilation mechanisms of a middle cerebral arteries (MCAs) in low salt and high salt fed Sprague-Dawley rats

Introduction: This pilot study aimed to determine the effects of carnosine supplementation on the mechanisms of flow-induced dilation (FID) in isolated middle cerebral arteries (MCAs) of Sprague-Dawley rats on LS and HS diet. Methods: Ten-weeks-old Sprague-Dawley rats (N=3-4 per group) were divided to low salt group (LS ; 0.4% NaCl in rodent chow), HS group (4% NaCl in rodent chow), LS+carnosine group (carnosine by oral gavage 150 mg/kg per day/7 days) and HS+carnosine group (oral gavage 150 mg/kg per day/7 days), fed for 1 week, water ad libidum. Rats were anesthetized with ketamine-chloride (75 mg/kg) and midazolam (0.5 mg/kg), decapitated and MCA was isolated, cannulated on glass pipettes and pressurized (DMT pressure myograph, Denmark). Reactivity of MCAs in response to stepwise increases in pressure gradients (Δ10-Δ100 mmHg) was determined in absence/presence of Dimethyl fumarate (DMF), the nuclear factor erythroid 2– related factor 2 (Nrf2) activator. The endothelium-independent response was tested using the NO donor sodium nitroprusside (SNP ; 10-6 mol/L) and endothelium-dependent vasodilation was tested using acetylcholine (ACh ; 10-6 mol/L). Statistical analyses were performed with Two-way ANOVA tests ; p<0.05 was considered significant. All experiments conformed to EU directive 86/609 and were approved by the local (No. 2158-61-46-22- 14, 2158-61-46-22-13) and national (355/2022, 356/2022) Ethical Committee. Results: FID was significantly reduced in HS group compared to LS group. FID was similar between the LS and LS +carnosine groups while carnosine administration in HS group restored FID at ∆40 -100 mm Hg. ACh-induced dilation was significantly decreased in HS group compared to the other study groups. SNP-induced vasodilation was preserved and similar in all groups. In HS group, DMF significantly increased FID at ∆40 mm Hg, while had no effect in other groups. Conclusion: Administration of carnosine restores vasodilation impaired by HS diet. HS diet might possibly suppress /inhibit Nrf2 pathway(s). Acknowledgements: This study was supported by the Faculty of Medicine Osijek Institutional grant IP- 1 (2020 ; PI Ines Drenjančević), IP3 (2021 ; PI Ines Drenjančević), IP1 (2022 ; PI Ines Drenjančević), IP16 (2022 ; PI Zrinka Mihaljević) and by European Structural and Investment Funds through a grant to the Croatian National Science Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek # KK.01.1.1.01.0010.

flow induced dilation, carnosine, Sprague-Dawley rats

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