Effects of high-cholesterol diet and parallel exercise training on the vascular function of rabbit aortas: a time course study

2003 ◽  
Vol 95 (3) ◽  
pp. 1194-1200 ◽  
Author(s):  
Ai-Lun Yang ◽  
Chauying J. Jen ◽  
Hsiun-ing Chen
Keyword(s):  
Nitric Oxide ◽  
Exercise Training ◽  
Vascular Function ◽  
Time Course ◽  
Early Stage ◽  
Elevated Serum ◽  
Normal Diet ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol

It is plausible to assume that exercise training, when applied early enough, can completely correct atherosclerotic defects. Using rabbit aortic specimens, we examined the effects of chronic exercise and high-cholesterol diet feeding on vascular function for different time periods. Male New Zealand White rabbits were divided into four groups: the normal diet groups with or without exercise training and the high-cholesterol diet groups with or without exercise training. Animals in high-cholesterol diet groups were fed 2% cholesterol rabbit chow for 2, 4, or 6 wk. Those in exercise training groups ran on a treadmill at 0.88 km/h for up to 40 min/day, 5 days/wk for the same period of time as the diet feeding. Thoracic aortas were isolated for functional and immunohistochemical analyses. We found that 1) although high-cholesterol diet feeding (≥2 wk) elevated serum cholesterol levels and impaired acetylcholine-evoked vasorelaxation, only the latter effect was reversed by exercise training; 2) the effects of diet and exercise on acetylcholine-evoked vasorelaxation were mainly due to altered release of nitric oxide and endothelium-derived hyperpolarizing factor; and 3) diet feeding for 4 or 6 wk caused significant lipid deposition and expression of P-selectin, VCAM-1, monocyte chemoattractant protein-1, and inducible nitric oxide synthase, which were largely reduced by exercise training. In conclusion, parallel exercise training almost completely reverses the early-stage endothelial dysfunction caused by high-cholesterol diet feeding.

Agonist-specific impairment of coronary vascular function in genetically altered, hyperlipidemic mice

1999 ◽  
Vol 276 (4) ◽  
pp. R1023-R1029 ◽  
Author(s):  
Kathryn G. Lamping ◽  
Daniel W. Nuno ◽  
David A. Chappell ◽  
Frank M. Faraci
Keyword(s):  
Nitric Oxide ◽  
Coronary Arteries ◽  
Guanylate Cyclase ◽  
Vascular Function ◽  
Soluble Guanylate Cyclase ◽  
Plasma Cholesterol ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Deficient Mice

The objectives of the present study were to 1) examine mechanisms involved in endothelium-dependent responses of coronary arteries from normal mice and 2) determine whether vascular responses of coronary arteries are altered in two genetic models of hypercholesterolemia [apolipoprotein E (apoE)-deficient mice (apoE −/−) and combined apoE and low-density lipoprotein receptor (LDLR)-deficient mice (apoE + LDLR −/−)]. Plasma cholesterol levels were higher in both apoE −/− and apoE + LDLR −/− compared with normal mice on normal and high-cholesterol diets (normal chow: normal 110 ± 5 mg/dl, apoE −/− 680 ± 40 mg/dl, apoE + LDLR −/− 810 ± 40 mg/dl; high-cholesterol chow: normal 280 ± 60 mg/dl, apoE −/− 2,490 ± 310 mg/dl, apoE + LDLR −/− 3,660 ± 290 mg/dl). Coronary arteries from normal (C57BL/6J), apoE −/−, and apoE + LDLR −/− mice were isolated and cannulated, and diameters were measured using videomicroscopy. In normal mice, vasodilation in response to ACh and serotonin was markedly reduced by 10 μM N ω-nitro-l-arginine (an inhibitor of nitric oxide synthase) or 20 μM 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ; an inhibitor of soluble guanylate cyclase). Vasodilation to nitroprusside, but not papaverine, was also inhibited by ODQ. Dilation of arteries from apoE −/− and apoE + LDLR −/− mice on normal diet in response to ACh was similar to that observed in normal mice. In contrast, dilation of arteries in response to serotonin from apoE −/− and apoE + LDLR −/− mice was impaired compared with normal. In arteries from both apoE −/− and apoE + LDLR −/− mice on high-cholesterol diet, dilation to ACh was decreased. In apoE + LDLR −/− mice on high-cholesterol diet, dilation of coronary arteries to nitroprusside was increased. These findings suggest that dilation of coronary arteries from normal mice in response to ACh and serotonin is dependent on production of nitric oxide and activation of soluble guanylate cyclase. Hypercholesterolemia selectively impairs dilator responses of mouse coronary arteries to serotonin. In the absence of both apoE and the LDL receptor, high levels of cholesterol result in a greater impairment in coronary endothelial function.

scholarly journals Albino mice with the point mutation at the tyrosinase locus show high cholesterol diet-induced NASH susceptibility

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaushalya Kulathunga ◽  
Arata Wakimoto ◽  
Yukiko Hiraishi ◽  
Manoj Kumar Yadav ◽  
Kyle Gentleman ◽  
...  
Keyword(s):  
Point Mutation ◽  
Genetic Difference ◽  
Elevated Serum ◽  
Serum Lipoprotein ◽  
Normal Diet ◽  
Lipid Absorption ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Alcoholic Fatty Liver

AbstractNon-alcoholic fatty liver disease (NAFLD) constitutes a metabolic disorder with high worldwide prevalence and increasing incidence. The inflammatory progressive state, non-alcoholic steatohepatitis (NASH), leads to liver fibrosis and carcinogenesis. Here, we evaluated whether tyrosinase mutation underlies NASH pathophysiology. Tyrosinase point-mutated B6 (Cg)-Tyrc-2J/J mice (B6 albino) and C57BL/6J black mice (B6 black) were fed with high cholesterol diet (HCD) for 10 weeks. Normal diet-fed mice served as controls. HCD-fed B6 albino exhibited high NASH susceptibility compared to B6 black, a phenotype not previously reported. Liver injury occurred in approximately 50% of B6 albino from one post HCD feeding, with elevated serum alanine aminotransferase and aspartate aminotransferase levels. NASH was induced following 2 weeks in severe-phenotypic B6 albino (sB6), but B6 black exhibited no symptoms, even after 10 weeks. HCD-fed sB6 albino showed significantly higher mortality rate. Histological analysis of the liver revealed significant inflammatory cell and lipid infiltration and severe fibrosis. Serum lipoprotein analysis revealed significantly higher chylomicron and very low-density lipoprotein levels in sB6 albino. Moreover, significantly higher small intestinal lipid absorption and lower fecal lipid excretion occurred together with elevated intestinal NPC1L1 expression. As the tyrosinase point mutation represents the only genetic difference between B6 albino and B6 black, our work will facilitate the identification of susceptible genetic factors for NASH development and expand the understanding of NASH pathophysiology.

Endothelial function in coronary arterioles from pigs with early-stage coronary disease induced by high-fat, high-cholesterol diet: effect of exercise

2004 ◽  
Vol 97 (3) ◽  
pp. 1159-1168 ◽  
Author(s):  
Kyle K. Henderson ◽  
James R. Turk ◽  
James W. E. Rush ◽  
M. Harold Laughlin
Keyword(s):  
Nitric Oxide ◽  
Cardiovascular Disease ◽  
Exercise Training ◽  
Endothelial Function ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
High Fat ◽  
Early Stages ◽  
Coronary Arterioles

Because hypercholesterolemia can attenuate endothelial function and exercise training can augment endothelial function, we hypothesized that exercise training would improve endothelial function of coronary arterioles from pigs in the early stages of cardiovascular disease induced by a high-fat, high-cholesterol (HF) diet. Yucatan miniature swine were fed a normal-fat (NF) diet or HF diet (2% cholesterol) for 20 wk in which 8 and 46% of their calories were derived from fat, respectively. Both groups were subdivided into sedentary (Sed) or exercise-trained (Ex) groups. This resulted in four experimental groups: NFSed, NFEx, HFSed, and HFEx. Endothelial function was assessed in coronary arterioles 75–100 μm in diameter dissected from the left ventricular apex. Responses to endothelial-dependent dilation induced by bradykinin (BK), ADP, and flow were similar in all four groups, whereas dilation to aggregating platelets in the presence of indomethacin and ketanserin was attenuated in HFSed arterioles ( P = 0.01). The attenuated response to aggregating platelets was prevented or reversed in HFEx arterioles ( P = 0.03). In HFSed arterioles, BK induced release of an indomethacin-sensitive prostanoid constrictor. In contrast, after exercise training, there was no evidence of this constrictor and BK-induced release of an indomethacin-sensitive prostanoid dilator in HFEx arterioles ( P = 0.04). Endothelial nitric oxide synthase protein in arterioles was significantly reduced in HF groups ( P < 0.05) and increased in Ex groups ( P < 0.05). Interestingly, the relative contribution of nitric oxide to BK-induced dilation, as assessed with nitro-l-arginine methyl ester, was similar in arterioles in the NF, HF, Sed, and Ex groups. These results suggest that, in the early stages of cardiovascular disease, a high-fat, high-cholesterol diet has modest effects on endothelial-dependent dilation in coronary arterioles; nonetheless, these effects are prevented or reversed with exercise training.

Effects of dietary flaxseed on vascular contractile function and atherosclerosis during prolonged hypercholesterolemia in rabbits

2006 ◽  
Vol 291 (6) ◽  
pp. H2987-H2996 ◽  
Author(s):  
C. M. C. Dupasquier ◽  
A.-M. Weber ◽  
B. P. Ander ◽  
P. P. Rampersad ◽  
S. Steigerwald ◽  
...  
Keyword(s):  
Vascular Function ◽  
Contractile Function ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Relaxation Response ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Beneficial Effects ◽  
Atherosclerotic Lesions

Dietary flaxseed has significant anti-atherogenic effects. However, the limits of this action and its effects on vascular contractile function are not known. We evaluated the effects of flaxseed supplementation on atherosclerosis and vascular function under prolonged hypercholesterolemic conditions in New Zealand White rabbits assigned to one of four groups for 6, 8, or 16 wk of feeding: regular diet (RG), 10% flaxseed-supplemented diet (FX), 0.5% cholesterol-supplemented diet (CH), and 0.5% cholesterol- and 10% flaxseed-supplemented diet (CF). Cholesterol feeding resulted in elevated plasma cholesterol levels and the development of atherosclerosis. The CF group had significantly less atherosclerotic lesions in the aorta and carotid arteries after 6 and 8 wk than the CH animals. However, the anti-atherogenic effect of flaxseed supplementation was completely attenuated by 16 wk. Maximal tension induced in aortic rings either by KCl or norepinephrine was not impaired by dietary cholesterol until 16 wk. This functional impairment was not prevented by including flaxseed in the high-cholesterol diet. Aortic rings from the cholesterol-fed rabbits exhibited an impaired relaxation response to acetylcholine at all time points examined. Including flaxseed in the high-cholesterol diet completely normalized the relaxation response at 6 and 8 wk and partially restored it at 16 wk. No significant changes in the relaxation response induced by sodium nitroprusside were observed in any of the groups. In summary, dietary flaxseed is a valuable strategy to limit cholesterol-induced atherogenesis as well as abnormalities in endothelial-dependent vasorelaxation. However, these beneficial effects were attenuated during prolonged hypercholesterolemic conditions.

SHORT TERM HIGH CHOLESTEROL DIET CAUSES CHANGES IN MEGAKARYOCYTE SIZE AND IN VASCULAR ULTRASTRUCTURE

1987 ◽  
Author(s):  
S Dalby Kristensen ◽  
K M Roberts ◽  
J Lawry ◽  
J F Martin
Keyword(s):  
Smooth Muscle ◽  
Normal Diet ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Short Term ◽  
Transmission Electron ◽  
Perfusion Fixation ◽  
And Migration ◽  
Proliferation And Migration

Platelets produced by megakaryocytes (MK) have a role in atherogenesis. Six pairs of male litter mate rabbits were randomised to feeding with either 2g of cholesterol daily in addition to their normal diet or normal diet alone. After seven days the animals were killed and serum cholesterol, platelet count, MK total, cytoplasmic and nuclear area (microscopic planimetry) and MK DNA content cell distribution (fluorescent activated cell sorting) were measured and compared between the two groups. The results are given in the table as medians with range values in brackets.After perfusion-fixation the aortas were examined by transmission electron microscopy. In the aortas from the animals on high cholesterol diet cells with ultrastructural features resembling smooth muscle cells were found in the intima. Changes in megakaryocyte size are associated with the occurrence of smooth muscle cell proliferation and migration. The platelet-megakaryocyte axis may be activated in early atherogenesis.

Dietary nitrite prevents hypercholesterolemic microvascular inflammation and reverses endothelial dysfunction

2009 ◽  
Vol 296 (5) ◽  
pp. H1281-H1288 ◽  
Author(s):  
Karen Y. Stokes ◽  
Tammy R. Dugas ◽  
Yaoping Tang ◽  
Harsha Garg ◽  
Eric Guidry ◽  
...  
Keyword(s):  
Drinking Water ◽  
Endothelial Dysfunction ◽  
Leukocyte Adhesion ◽  
Normal Diet ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Cytoprotective Activity ◽  
Reactive Protein ◽  
Microvascular Inflammation

The nitrite anion is an endogenous product of mammalian nitric oxide (NO) metabolism, a key intermediate in the nitrogen cycle in plants, and a constituent of many foods. Research over the past 6 years has revealed surprising biological and cytoprotective activity of this anion. Hypercholesterolemia causes a proinflammatory phenotype in the microcirculation. This phenotype appears to result from a decline in NO bioavailability that results from a reduction in NO biosynthesis, inactivation of NO by superoxide, or both. Since nitrite has been shown to be potently cytoprotective and restore NO biochemical homeostasis, we investigated if supplemental nitrite could attenuate microvascular inflammation caused by a high cholesterol diet. C57Bl/6J mice were fed either a normal diet or a high cholesterol diet for 3 wk to induce microvascular inflammation. Mice on the high cholesterol diet received either nitrite-free drinking water or supplemental nitrite at 33 or 99 mg/l ad libitum in their drinking water. The results from this investigation reveal that mice fed a cholesterol-enriched diet exhibited significantly elevated leukocyte adhesion to and emigration through the venular endothelium as well as impaired endothelium-dependent relaxation in arterioles. Administration of nitrite in the drinking water inhibited the leukocyte adhesion and emigration and prevented the arteriolar dysfunction. This was associated with sparing of reduced tetrahydrobiopterin and decreased levels of C-reactive protein. These data reveal novel anti-inflammatory properties of nitrite and implicate the use of nitrite as a new natural therapy for microvascular inflammation and endothelial dysfunction associated with hypercholesterolemia.

scholarly journals A High-Cholesterol Diet Increases Toll-like Receptors and Other Harmful Factors in the Rabbit Myocardium: The Beneficial Effect of Statins

2021 ◽  
Vol 43 (2) ◽  
pp. 818-830
Author(s):  
Alkistis Kapelouzou ◽  
Michalis Katsimpoulas ◽  
Christos Kontogiannis ◽  
Irene Lidoriki ◽  
Georgios Georgiopoulos ◽  
...  
Keyword(s):  
Normal Diet ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Control Groups ◽  
Reverse Transcription Pcr ◽  
Rabbit Myocardium ◽  
Normal Chow ◽  
Polymerase Chain

Background: A high-cholesterol diet (HCD) induces vascular atherosclerosis through vascular inflammatory and immunological processes via TLRs. The aim of this study is to investigate the mRNA expression of TLRs and other noxious biomarkers expressing inflammation, fibrosis, apoptosis, and cardiac dysfunction in the rabbit myocardium during (a) high-cholesterol diet (HCD), (b) normal diet resumption and (c) fluvastatin or rosuvastatin treatment. Methods: Forty-eight male rabbits were randomly divided into eight groups (n = 6/group). In the first experiment, three groups were fed with HCD for 1, 2 and 3 months. In the second experiment, three groups were fed with HCD for 3 months, followed by normal chow for 1 month and administration of fluvastatin or rosuvastatin for 1 month. Control groups were fed with normal chow for 90 and 120 days. The whole myocardium was removed; total RNA was isolated from acquired samples, and polymerase chain reaction, reverse transcription PCR and quantitative real-time PCR were performed. Results: mRNA of TLRs 2, 3, 4 and 8; interleukin-6; TNF-a; metalloproteinase-2; tissue inhibitor of metalloproteinase-1; tumor protein 53; cysteinyl aspartate specific proteinase-3; and brain natriuretic peptide (BNP) increased in HCD. Statins but not resumption of a normal diet decreased levels of these biomarkers and increased levels of antifibrotic factors. Conclusions: HCD increases the levels of TLRs; inflammatory, fibrotic and apoptotic factors; and BNP in the rabbit myocardium. Atherogenic diets adversely affect the myocardium at a molecular level and are reversed by statins.

scholarly journals High-cholesterol diet during pregnancy induces maternal vascular dysfunction in mice: potential role for oxidized LDL-induced LOX-1 and AT1 receptor activation

2020 ◽  
Vol 134 (17) ◽  
pp. 2295-2313
Author(s):  
Tamara Sáez ◽  
Floor Spaans ◽  
Raven Kirschenman ◽  
Tatsuya Sawamura ◽  
Sandra T. Davidge
Keyword(s):  
Vascular Function ◽  
Vascular Dysfunction ◽  
Oxidized Ldl ◽  
Receptor Activation ◽  
Adverse Outcomes ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Uterine Arteries ◽  
Vascular Beds

Abstract The lectin-like oxidized low-density-lipoprotein (oxLDL) receptor-1 (LOX-1) has been shown to induce angiotensin II (AngII) type 1 receptor (AT1) activation, contributing to vascular dysfunction. Preeclampsia is a pregnancy complication characterized by vascular dysfunction and increased LOX-1 and AT1 activation; however, whether LOX-1 and AT1 activity contributes to vascular dysfunction in preeclampsia is unknown. We hypothesized that increased oxLDL levels during pregnancy lead to LOX-1 activation and subsequent AT1 activation, resulting in vascular dysfunction. Pregnant wild-type (WT) and transgenic LOX-1 overexpressing (LOX-1tg) mice were fed a control diet (CD) or high-cholesterol diet (HCD, to impair vascular function) between gestational day (GD) 13.5-GD18.5. On GD18.5, AngII-induced vasoconstriction and methylcholine (MCh)-induced endothelium-dependent vasodilation responses were assessed in aortas and uterine arteries. HCD decreased fetal weight and increased circulating oxLDL/cholesterol levels in WT, but not in LOX-1tg mice. HCD did not alter AngII responsiveness or AT1 expression in both vascular beds; however, AngII responsiveness and AT1 expression were lower in aortas from LOX-1tg compared with WT mice. In aortas from WT-CD mice, acute oxLDL exposure induced AT1-mediated vasoconstriction via LOX-1. HCD impaired endothelium-dependent vasodilation and increased superoxide levels in WT aortas, but not uterine arteries. Moreover, in WT-CD mice oxLDL decreased MCh sensitivity in both vascular beds, partially via LOX-1. In summary, HCD impaired pregnancy outcomes and vascular function, and oxLDL-induced LOX-1 activation may contribute to vascular dysfunction via AT1. Our study suggests that LOX-1 could be a potential target to prevent adverse outcomes associated with vascular dysfunction in preeclampsia.

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