Short‐term very low caloric intake causes endothelial dysfunction and increased susceptibility to cardiac arrhythmias and pathology in male rats

Abstract

New Findings What is the central question of this study? What are the effects of a 2 week period of severe food restriction on vascular reactivity of resistance arteries and on cardiac structure and function? What is the main finding and its importance? This study showed, for the first time, that a 2 week period of severe food restriction in adult male Fischer rats caused endothelial dysfunction in mesenteric arteries and increased the susceptibility to ischaemia–reperfusion‐induced arrhythmias and cardiac pathology. Our findings might have ramifications for cardiovascular risk in people who experience periods of inadequate caloric intake. Abstract Severe food restriction (sFR) is a common dieting strategy for rapid weight loss. Male Fischer rats were maintained on a control (CT) or sFR (40% of CT food intake) diet for 14 days to mimic low‐calorie crash diets. The sFR diet reduced body weight by 16%. Haematocrits were elevated by 10% in the sFR rats, which was consistent with the reduced plasma volume. Mesenteric arteries from sFR rats had increased sensitivity to vasoconstrictors, including angiotensin II [maximum (%): CT, 1.30 ± 0.46 versus sFR, 11.5 ± 1.6; P < 0.0001; n = 7] and phenylephrine [maximum (%): CT, 78.5 ± 2.8 versus sFR, 94.5 ± 1.7; P < 0.001; n = 7] and reduced sensitivity to the vasodilator acetylcholine [EC 50 (n m ): CT, 49.2 ± 5.2 versus sFR, 71.6 ± 6.8; P < 0.05; n = 7]. Isolated hearts from sFR rats had a 1.7‐fold increase in the rate of cardiac arrhythmias in response to ischaemia–reperfusion and more cardiac pathology, including myofibrillar disarray with contractions and cardiomyocyte lysis, than hearts from CT rats. The sFR dietary regimen is similar to very low‐calorie commercial and self‐help weight‐loss programmes, which provide ∼800–1000 kcal day −1 . Therefore, these findings in rats warrant the study of cardiovascular function in individuals who engage in extreme dieting or are subjected to bouts of very low caloric intake for other reasons, such as socioeconomic factors and natural disasters.

Caloric restriction reduces sympathetic activity similar to beta-blockers but conveys additional mitochondrio-protective effects in aged myocardium

“…Furthermore, the application of a CR even more severe than in our study may mediate direct negative effects even in healthy individuals. Indeed, a 60% reduction in calories was recently shown to cause endothelial dysfunction and cardiac arrhythmia in rats 56 . Furthermore, severe CR was also reported to result in an increased activation of central RAAS in order to maintain blood pressure allostasis 57 and in myocardial dysfunction due to impaired cardiac calcium handling in rats 58 .…”

Susceptibility of female rats to cardiac arrhythmias following refeeding after severe food restriction

“…After the isolated heart experiment, cardiac tissue was fixed for histology and morphology as we previously described [ 4 ]. In brief, fixed tissue sections were subjected to hematoxylin/eosin (H&E) and Masson’s trichrome staining .…”

“…In this model, rats are maintained for 2 weeks on a severe caloric restricted (sFR) diet, in which normal daily caloric intake is reduced by 60%. Both female [ 3 ] and male [ 4 ] rats lose approximately 15% of their BW under these dietary conditions. At the end of the 2-week period, the sFR rats exhibit hypotension and bradycardia, which is also observed in people experiencing similar degrees of caloric restriction [ 3 , 5 ].…”

“…More recently, we showed that isolated hearts from M-sFR rats exhibited more cardiac pathology including myofibrillar disarray with contractions and cardiomyocyte lysis than hearts from the control group (M-CT) [ 4 ]. Not only did the M-sFR hearts exhibit cardiac pathology, they were also more susceptible to ventricular arrhythmias induced by ischemia/reperfusion (I/R).…”

Impact of Dietary Restriction Regimens on Mitochondria, Heart, and Endothelial Function: A Brief Overview

“…However, a short period (2 weeks) of severe food restriction in rats was responsible for endothelial dysfunction in mesenteric arteries and for ischemia-reperfusion-induced arrhythmias and cardiac pathology (Almeida et al, 2020 ).…”