engleski

The influence of high salt intake on carotid arteries responses to acetylcholine and changes in flow in child type (WT) 129/SV and TFF3-/- mice

High salt (HS) diet leads to endothelial dysfunction and impaired vascular reactivity to various stimuli. Different strains of rats, including genetically altered are the most frequent experimental models used for HS vascular functional studies (1, 2, 3) Hereby we introduce new model of transgenic TFF3-/- mice which have favorable ratio of ω-6/ω-3 free fatty acids and modified metabolism of arachidonic acid (AA) (4, 5). Considering the importance of metabolites of AA in vascular responses to stimuli, TFF3-/- mice may give valuable information on the impact of HS diet of vascular function related to AA metabolism. The aim of this study was to assess the effects of 1 week HS diet on acetylcholine (10-6 M), SNP (10-6 M) and flow-induced response (FIR) in isolated, pressurized carotid arteries of TFF3-/- and their wild type controls, WT 129/Sv mice. 9-weeks old TFF3-/- and WT 129/Sv mice (both sexes) were divided in LS group (N=4 + 4) fed with standard rat chow (0.4% NaCl) and HS group (N=5 + 4) fed food containing 4% NaCl for 1 week. Mice were anesthetized with ketamin- klorid (100 mg/kg) and midazolam (5 mg/kg) and decapitated. Carotid arteries were isolated, cannulated and pressurized for 60’at 100 mmHg to assess basal diameter and than subjected to flow at pressure gradients from Δ10-Δ180 mmHg (DMT pressure myograph, Danmark). To test differences among groups Two-way ANOVA was used, p<0.05 considered significant. All experimental procedures conformed to the EU Guidelines (Directive 86/609) and national laws were approved by local and national Ethical Committee (Class:UP/I-322-01/14-01/36, No. 525- 10/0255-15-6). In each group (LS or HS) FIR at pressure gradients from Δ10-Δ60 mmHg leads to constriction of vessels while FIR at pressure gradients from Δ100-Δ180 mmHg leads to dilation of vessels compared to baseline (Δ0 mmHg). TFF3-/- HS group did not significantly differ in FIR compared to TFF3-/- LS group. Carotid arteries of WT 129/Sv-HS mice exhibited increase in constriction at Δ60 mmHg (p<0.05) and reduced dilation at pressure gradients from Δ100- Δ160 mmHg (p<0.05) compared to its LS control group. Both, TFF3-/- HS and WT 129/Sv HS groups had reduced response to ACh compared to their respective controls. SNP response was preserved in all tested groups. FIR of TFF3-/- LS vs. 129/Sv LS mice and TFF3-/- HS vs. 129/Sv HS mice did not show significant differences (p>0.05). These preliminary results show that FIR differs from ACh-induced responses. ACh- induced dilation was abolished, while FIR was preserved in TFF3-/- HS groups. HS intake seems to have smaller impact on FIR in TFF3-/- mice compared to their WT controls possibly due to favorable fatty acid composition and their direct or indirect role in production of vasoactive metabolites mediating FIR. 1) Cosic A, Jukic I, Stupin A, Mihalj M, Mihaljevic Z, Novak S, Vukovic R, Drenjancevic I. Attenuated flow- induced dilation of middle cerebral arteries is related to increased vascular oxidative stress in rats on a short-term high salt diet. J Physiol. 2016 Apr 8. doi: 10.1113/ JP272297. 2) Drenjancevic-Peric I, Lombard JH. Reduced angiotensin II and oxidative stress contribute to impaired vasodilation in Dahl salt-sensitive rats on low-salt diet. Hypertension. 2005 Apr ; 45(4):687-91. Epub 2005 Feb 14. 3) Durand MJ, Lombard JH. Low-dose angiotensin II infusion restores vascular function in cerebral arteries of high salt-fed rats by increasing copper/zinc superoxide dimutase expression. Am J Hypertens. 2013 ; 26(6):739-47. doi: 10.1093/ajh/hpt015. Epub 2013 Feb 26. 4) Mihalj M, Bujak M, Tartaro Bujak I., Tolušic´ Levak M, Miskovic K, Kopacin V, Mihaljevic B, Drenjancevic I, Baus-Loncar M. Mice lacking trefoil family factor 3 gene present with reduced rate of monounsaturated fatty acids in the liver (abstract). Physiology 2014 (London, UK) PCA172 5) Bujak M, Mihalj M, Tartaro Bujak I, Vucˇinic´ S, Horvatic´ A, Novak S, Miskovic´ K, Kopacˇin V, Mihaljevic´ B, Drenjancˇevic´ I, Baus Loncˇar M. Fatty acid and protein profiling in the liver of Tff2 and Tff3 deficient mice // 7th International Conference on Trefoil Factor Family Peptides Abstract booklet, Erlangen, Germany, 2015 Supported by grant from Croatian Science Fundation #IP- 2014-09-6380 Where applicable, the authors confirm that the experiments described here conform with the Physiological Society ethical requirements.

high salt diet ; flow induced dilation ; carotid arteries ; transgenic TFF3-/- mice

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