Intermittent fasting (IF) represents one of the dietary regimens being effectively used in non-pharmacological prevention and treatment of cardiometabolic disorders. The aim of the present study was to detect the retained alterations at the level of arterial function caused by a 5-week-lasting period of IF in adult male Wistar-Kyoto rats after their switching back to ordinary feeding (4 weeks of ad libitum regimen). The rats were administered a diet containing normal or high percentage of fat. Control rat groups were fed continuously ad libitum. The decreased weekly calorie intake in rats during IF period was associated with the discontinuation of body weight gain, irrespective of the type of diet; moreover, rats fed with a high-fat diet had significantly increased systolic blood pressure in comparison with the other groups. At the end of the experiment, large and small arteries were isolated from the rats and arterial rings with intact or removed perivascular adipose tissue (PVAT) were prepared for isometric tension recording. In the rat groups exposed to IF period, the aorta rings with intact PVAT showed a significant increase in relaxation responses when compared to groups without IF. The effect of IF was also manifested in the increase in sensitivity of arterial preparations to noradrenaline which was, however, mostly attenuated by the enhanced anticontractile influence of PVAT. These results indicate that the improvement of PVAT properties could represent one of the mechanisms by which IF-induced beneficial effects on vascular function might be preserved even after the return to ad libitum regimen.

Institute of Normal and Pathological Physiology Centre of Experimental Medicine Slovak Academy of Sciences Bratislava Slovakia

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Longo VD, Mattson MP. Fasting: molecular mechanisms and clinical applications. Cell Metab. 2014;19:181–192. doi: 10.1016/j.cmet.2013.12.008. PubMed DOI PMC

Zou MH, Wu Y. AMP-activated protein kinase activation as a strategy for protecting vascular endothelial function. Clin Exp Pharmacol Physiol. 2008;35:535–545. doi: 10.1111/j.1440-1681.2007.04851.x. PubMed DOI PMC

de Cabo R, Mattson MP. Effects of intermittent fasting on health, aging, and disease. N Engl J Med. 2019;381:2541–2551. doi: 10.1056/NEJMra1905136. PubMed DOI

Rodríguez C, Muñoz M, Contreras C, Prieto D. AMPK, metabolism, and vascular function. FEBS J. 2021;288:3746–3771. doi: 10.1111/febs.15863. PubMed DOI

Huang Z, Wu M, Zeng L, Wang D. The beneficial role of Nrf2 in the endothelial dysfunction of atherosclerosis. Cardiol Res Pract. 2022;2022:4287711. doi: 10.1155/2022/4287711. PubMed DOI PMC

Citrin KM, Chaube B, Fernández-Hernando C, Suárez Y. Intracellular endothelial cell metabolism in vascular function and dysfunction. Trends Endocrinol Metab. 2025;36:744–755. doi: 10.1016/j.tem.2024.11.004. PubMed DOI PMC

Mattson MP. The cyclic metabolic switching theory of intermittent fasting. Nat Metab. 2025;7:665–678. doi: 10.1038/s42255-025-01254-5. PubMed DOI

Lin Y, Wang Y, Li PF. PPARα: An emerging target of metabolic syndrome, neurodegenerative and cardiovascular diseases. Front Endocrinol (Lausanne) 2022;13:1074911. doi: 10.3389/fendo.2022.1074911. PubMed DOI PMC

Kvandová M, Rajlic S, Stamm P, Schmal I, Mihaliková D, Kuntic M, Bayo Jimenez MT, et al. Mitigation of aircraft noise-induced vascular dysfunction and oxidative stress by exercise, fasting, and pharmacological α1AMPK activation: molecular proof of a protective key role of endothelial α1AMPK against environmental noise exposure. Eur J Prev Cardiol. 2023;30:1554–1568. doi: 10.1093/eurjpc/zwad075. PubMed DOI

Cui J, Lee S, Sun Y, Zhang C, Hill MA, Li Y, Zhang H. Alternate day fasting improves endothelial function in type 2 diabetic mice: role of adipose-derived hormones. Front Cardiovasc Med. 2022;9:925080. doi: 10.3389/fcvm.2022.925080. PubMed DOI PMC

Graham EL, Weir TL, Gentile CL. Exploring the impact of intermittent fasting on vascular function and the immune system: a narrative review and novel perspective. Arterioscler Thromb Vasc Biol. 2025;45:654–668. doi: 10.1161/ATVBAHA.125.322692. PubMed DOI PMC

Ahmet I, Wan R, Mattson MP, Lakatta EG, Talan M. Cardioprotection by intermittent fasting in rats. Circulation. 2005;112:3115–3121. doi: 10.1161/CIRCULATIONAHA.105.563817. PubMed DOI

Demirci E, Çalapkorur B, Celik O, Koçer D, Demirelli S, Şimsek Z. Improvement in blood pressure after intermittent fasting in hipertension: could renin-angiotensin system and autonomic nervous system have a role? Arq Bras Cardiol. 2023;120:e20220756. doi: 10.36660/abc.20220756. PubMed DOI PMC

Kjærulff MLG, Luong TV, Munk OL, Tolbod LP, Cunnane SC, Nielsen EN, Berg-Hansen K, et al. Three-week alternate day fasting improves myocardial flow reserve and reduces oxygen use in individuals with overweight. J Clin Endocrinol Metab. 2025:dgaf484. doi: 10.1210/clinem/dgaf484. PubMed DOI

Bencze M, Behuliak M, Vavřínová A, Zicha J. Altered contractile responses of arteries from spontaneously hypertensive rat: The role of endogenous mediators and membrane depolarization. Life Sci. 2016;166:46–53. doi: 10.1016/j.lfs.2016.10.005. PubMed DOI

Wan R, Ahmet I, Brown M, Cheng A, Kamimura N, Talan M, Mattson MP. Cardioprotective effect of intermittent fasting is associated with an elevation of adiponectin levels in rats. J Nutr Biochem. 2010;21:413–417. doi: 10.1016/j.jnutbio.2009.01.020. PubMed DOI PMC

Nicoll R, Henein MY. Caloric restriction and its effect on blood pressure, heart rate variability and arterial stiffness and dilatation: a review of the evidence. Int J Mol Sci. 2018;19:751. doi: 10.3390/ijms19030751. PubMed DOI PMC

Azemi AK, Siti-Sarah AR, Mokhtar SS, Rasool AHG. Time-restricted feeding improved vascular endothelial function in a high-fat diet-induced obesity rat model. Vet Sci. 2022;9:217. doi: 10.3390/vetsci9050217. PubMed DOI PMC

Varkaneh Kord H, Tinsley MG, Santos OH, Zand H, Nazary A, Fatahi S, Mokhtari Z, et al. The influence of fasting and energy-restricted diets on leptin and adiponectin levels in humans: A systematic review and meta-analysis. Clin Nutr. 2021;40:1811–1821. doi: 10.1016/j.clnu.2020.10.034. PubMed DOI

Tavakoli A, Bideshki MV, Zamani P, Tavakoli F, Dehghan P, Gargari BP. The effectiveness of fasting regimens on serum levels of some major weight regulating hormones: a GRADE-assessed systematic review and meta-analysis in randomized controlled trial. J Health Popul Nutr. 2025;44:104. doi: 10.1186/s41043-025-00834-1. PubMed DOI PMC

Zhu W, Cheng KK, Vanhoutte PM, Lam KS, Xu A. Vascular effects of adiponectin: molecular mechanisms and potential therapeutic intervention. Clin Sci (Lond) 2008;114:361–374. doi: 10.1042/CS20070347. PubMed DOI

Muffová B, Králová Lesná I, Poledne R. Physiology and pathobiology of perivascular adipose tissue: inflammation-based atherogenesis. Physiol Res. 2024;73:929–941. doi: 10.33549/physiolres.935384. PubMed DOI PMC

Ma J, Cheng Y, Su Q, Ai W, Gong L, Wang Y, Li L, et al. Effects of intermittent fasting on liver physiology and metabolism in mice. Exp Ther Med. 2021;22:950. doi: 10.3892/etm.2021.10382. PubMed DOI PMC

Kovář J, Poledne R. Nutrient-induced changes of liver fat content in humans. Physiol Res. 2025;74:163–174. doi: 10.33549/physiolres.935525. PubMed DOI PMC

Srivastava N, Kizhakkevalappil SP, Gupta S, Tyagi A, Srivastava S. Effect of intermittent fasting on cardiovascular autonomic regulation in healthy adults. J Heart Valve Dis. 2025;30:9–12.

Atrooz F, Alkadhi KA, Salim S. Understanding stress: Insights from rodent models. Curr Res Neurobiol. 2021;2:100013. doi: 10.1016/j.crneur.2021.100013. PubMed DOI PMC

Dallman MF, Akana SF, Bhatnagar S, Bell ME, Choi S, Chu A, Horsley C, Levin N, Meijer O, Soriano LR, Strack AM, Viau V. Starvation: early signals, sensors, and sequelae. Endocrinology. 1999;140:4015–4023. doi: 10.1210/endo.140.9.7001. PubMed DOI

Bucaktepe PGE, Akdağ M, Dasdag S, Celepkolu T, Yılmaz MA, Demir V, Haris P. Catecholamine levels in a Ramadan fasting model in rats: a case control study. Biotechnol Biotechnol Equip. 2016;30:706–712. doi: 10.1080/13102818.2016.1172510. DOI