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The effect of chronic treatment with fermented milk products containing bioactive tripeptides and plant sterols on blood pressure and vascular function was investigated in spontaneously hypertensive rats (SHR). Six-weeks old male SHR (n=36) were randomized into 4 groups by body weight and blood pressure to receive either Lactobacillus helveticus fermented standard milk product (containing tripeptides Ile-Pro-Pro, Val-Pro-Pro and Leu-Pro-Pro), test product with enzymatically produced tripeptides without or with plant sterols or control product without the active constituents for 8 weeks. Systolic blood pressure (SBP) was measured weekly using the tail-cuff method. Thoracic aorta and mesenteric artery were excised for vascular response measurements. At the end, SBP values vs. control product group were: standard product group -14 mmHg (P<0.05), test product group -12 mmHg and test product +sterols group -7 mmHg. The average daily tripeptide dose was 2.8-5.2 mg/kg. Total serum cholesterol in the test product +sterols group tended to be lower than in the test product group (P=0.10) whereas serum plant sterol (campesterol, sitosterol) concentrations were higher (P<0.001). In conclusion, bioactive tripeptide-containing milk products attenuated the blood pressure development in SHR. The plant sterols did not improve this effect. Vascular responses did not markedly differ between the groups, except that endothelium-derived hyperpolarizing factor (EDHF) -related aortic relaxation was demonstrated in the test product +sterols group.
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Diabetes is associated with endothelial dysfunction and platelet activation, both of which contribute to increased cardiovascular risk. We investigated whether the selective mineralocorticoid receptor (MR) antagonist eplerenone improves endothelial dysfunction and reduces platelet activation in diabetic rats. Male Wistar-rats were injected with streptozotocin (50 mg/kg i.v.) to induce insulin-deficient diabetes. After 2 weeks, treatment with eplerenone (100 mg/kg/day) or vehicle was initiated for 2 weeks. Aortic superoxide production determined by lucigenin-enhanced chemiluminescence and 2-hydroxyethidium formation was significantly increased in rats with diabetes and reduced by treatment with eplerenone (chemiluminescence: control 2045±227, STZ-placebo 3977±340, p<0.05 vs. control, STZ-eplerenone 1762±307, p<0.05 vs. STZ-placebo). Endothelium-dependent vasorelaxation was significantly attenuated in diabetic rats and was normalized by eplerenone (maximum relaxation in % of precontraction: control 95±3, STZ-placebo 82±3, p<0.01 vs. control, STZ-eplerenone 99±1, p<0.01 vs. STZ-placebo). Treatment with the selective MR antagonist significantly reduced fibrinogen-binding on activated GPIIb/IIIa (immunofluorescence: control 161±7, STZ-placebo 208±16, p<0.05 vs. control, STZ-eplerenone 173±6, p<0.05 vs. STZ-placebo). Eplerenone improves endothelial function by reducing superoxide formation and increasing NO bioavailability in diabetic rats. Platelet activation was significantly reduced by eplerenone. Selective MR blockade may constitute a useful therapeutic approach for treatment of vascular dysfunction in diabetes.
The study investigated the effect of chronic crowding stress on vascular function and nitric oxide (NO) production in rats with various family history of hypertension. Wistar (W), wBHR (offspring of W dams and spontaneously hypertensive sires), sBHR (offspring of spontaneously hypertensive dams and W sires) and spontaneously hypertensive rats (SHR) were used. Twelve-week-old males were divided into the control or crowded group for eight weeks. Basal blood pressure (BP, determined by tail-cuff plethysmography) of W, wBHR, sBHR and SHR rats was 112 ± 3, 129 ± 2, 135 ± 2 and 187 ± 3 mmHg, respectively. Crowding increased BP and reduced aortic NO synthase activity only in sBHR and SHR rats, without alterations in hypothalamic NO production. Acetylcholine-induced vasorelaxation of the femoral artery of stress-exposed rats was improved in W, unaltered in wBHR and sBHR and reduced in SHR. Crowding reduced serotonin-induced vasoconstriction in W and wBHR rats but had no effect in sBHR and SHR rats. In conclusion, the results suggest that crowded offspring of normotensive mothers were able to modify their vascular function in order to maintain BP at normal levels. On the other hand, offspring of hypertensive mothers were unable of effective adaptation of vascular function in stressful conditions resulting in gradual development of hypertension.
The beneficial cardiovascular effects of soy protein have been studied intensively in recent years. Another protein-rich legume is lupin, which has been shown to have similar effects to those of soy in lowering serum cholesterol levels. In this study we compared the effects of lupin and soy protein on hypertension and vascular functions in spontaneously diabetic Goto-Kakizaki (GK) rat, which develop hypertension when fed a high-salt diet. The rats were fed with a 6% NaCl diet containing either lupin or soy protein isolate (20% weight/weight) for two weeks. In the end of the study the SBP was 18.6 mmHg lower (p<0.001) in the lupin group, and 12.0 mmHg lower (p<0.01) in the soy group than in the control group. Lupin and soy treatments normalised the decreased vasocontraction observed in the NaCl-fed control group, but only lupin treatment improved the impaired endothelium-dependent vasorelaxation. The attenuation of hypertension is likely to be mediated by the corrected vascular dysfunction, whose precise mechanism and the possible clinical relevance remains to be studied further.
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Adipocytokines - novel link between inflammation and vascular funktion?

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Obesity and obesity related diseases are a major public health problem. Recent studies have shown that fat tissue is not a simple energy storage organ, but exerts important endocrine and immune functions. These are achieved predominantly through release of adipocytokines, which include several novel and highly active molecules released abundantly by adipocytes like leptin, resistin, adiponectin or visfatin, as well as some more classical cytokines released possibly by inflammatory cells infiltrating fat, like TNF-alpha, IL-6, MCP-1 (CCL-2), IL-1. All of those molecules may act on immune cells leading to local and generalized inflammation and may also affect vascular (endothelial) function by modulating vascular nitric oxide and superoxide release and mediating obesity related vascular disorders (including hypertension, diabetes, atherosclerosis, and insulin resistance) but also cancer or non-alcoholic fatty liver diseases. Present review, in a concise form, focuses on the effects of major adipocytokines, characteristic for adipose tissue like leptin, adiponectin, resistin and visfatin on the immune system, particularly innate and adaptive immunity as well as on blood vessels. Macrophages and T cells are populating adipose tissue which develops into almost an organized immune organ. Activated T cells further migrate to blood vessels, kidney, brain and other organs surrounded by infiltrated fat leading to their damage, thus providing a link between metabolic syndrome, inflammation and cardiovascular and other associated disorders. Ceretain treatments may lead to significant changes in adipocytokine levels. For example include beta-2 adrenoreceptor agonists, thiazolidinediones as well as androgens lead to decrease of plasma leptin levels. Moreover future treatments of metabolic system associated disorders should focus on the regulation of adipocytokines and their modes of action.
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