1. The present study evaluated the effect of diabetes, hypercholesterolaemia and their combination on the contribution of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) to relaxation of rat isolated aortic rings and the potential contribution of oxidant stress to the disturbance of endothelial function. 2. Thoracic aortic rings from control, diabetic, hypercholesterolaemic and diabetic plus hypercholesterolaemic rats were suspended in organ baths for tension recording. Generation of superoxide by the aorta was measured using lucigenin-enhanced chemiluminescence. 3. The maximal response to acetylcholine (ACh) was significantly reduced in diabetic or hypercholesterolaemic rats compared with control rats. In rats with diabetes plus hypercholesterolaemia, both the sensitivity and maximal response to ACh was impaired. In control rats, the response to ACh was abolished by the NO synthase inhibitor N(G)-nitro-L-arginine (L-NNA) or inhibition of soluble guanylate cyclase with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). In contrast, in rats with diabetes, hypercholesterolaemia or both, relaxation to ACh was resistant to inhibition by L-NNA or ODQ, but abolished by additional inhibition of K(Ca) channels with charybdotoxin plus apamin. 4. The generation of superoxide was not significantly enhanced in aortic rings from either diabetic or hypercholesterolaemic rats, but was significantly increased in aortic rings from rats with diabetes plus hypercholesterolaemia. 5. These results suggest that when diabetes and hypercholesterolaemia impair endothelium-dependent relaxation, due to a diminished contribution from NO, a compensatory contribution of EDHF to endothelium-dependent relaxation of the aorta is revealed. The attenuation of NO-mediated relaxation, at least in the presence of both diabetes and hypercholesterolaemia, is associated with enhanced superoxide generation.

Hypercholesterolaemia is associated with oxidative stress and endothelial dysfunction and leads to the development of atherosclerosis. Naringin exhibits cardiovascular protective and antioxidant properties. Therefore, the aim of this study was to assess the effect of naringin administration on vascular oxidative stress and endothelial dysfunction in hypercholesterolaemic rats and to elucidate its underlying mechanism. Sprague Dawley rats were fed a diet with 1.5% cholesterol (HCD) for 8 weeks to induce hypercholesterolaemia. Naringin (100 mg/kg body weight) was orally administrated to rats during the last 4 weeks of the diet treatment. After 8 weeks, the thoracic aorta was isolated to determine vascular function and nitric oxide (NO) levels. The aortic superoxide anion (O2−) level was detected using dihydroethidium (DHE) fluorescence staining. Protein expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, and inducible nitric oxide synthase (iNOS), as well as oxidative damage markers, was also evaluated in aortae. Naringin treatment of hypercholesterolaemic rats enhanced aortic NO levels, restored endothelium-dependent responses to acetylcholine (ACh), and reduced aortic O2− levels. Furthermore, naringin treatment decreased LOX-1, NADPH oxidase subunits (p47phox, Nox2, and Nox4), and iNOS as well as oxidative damage markers (3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE)) expression in aortic tissues from hypercholesterolaemic rats. These results demonstrate that naringin treatment improves endothelium dysfunction in hypercholesterolaemic rats, at least partially by decreasing oxidative stress via downregulation of LOX-1 and NADPH oxidase.

Background Hypercholesterolemia is a major risk factor for cardiovascular disease. It has been reported that pineapple contains healthy nutrients and phytochemicals associated with antioxidant and anti-inflammatory capacities. No investigation exists concerning the effect of pineapple consumption modulating hypercholesterolemia-induced cardiac damage in high-cholesterol diet (HCD)-fed rats. This study evaluated the effect of pineapple consumption on lipid-lowering, cardiac oxidative stress and inflammation in HCD-fed rats. Methods Male Sprague–Dawley rats were fed with HCD, in the presence and absence of Pineapple (Ananas comosus L.) cv. Pattavia powder for 8 weeks. Then, serum lipid profiles, liver and renal function tests, cardiac oxidative stress and pro-inflammatory cytokines were determined. Results Daily pineapple consumption reduced weight gain, serum lipid profiles, atherogenic coefficient (AC), cardiac risk ratio (CRR), and liver enzyme activity, without causing renal dysfunction. Pineapple consumption also restores cardiac protein carbonyl (cPC) content, reduces cardiac malondialdehyde (MDA), cardiac pro-inflammation cytokine IL-6 and IL-1β levels. Conclusion Pineapple possesses antioxidant and lipid-lowering properties and daily consumption alleviates hypercholesterolemia-induced cardiac lipid peroxidation and pro-inflammation elevation in an in vivo model. This study demonstrates that pineapple is a potential candidate for cardioprotection against hypercholesterolemia.

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