Short-term effects of glucosyl hesperidin and hesperetin on blood pressure and vascular endothelial function in spontaneously hypertensive rats

Glucosyl hesperidin (G-hesperidin) is a water-soluble derivative of hesperidin. In the present study, the short-term effects of G-hesperidin and hesperetin, a putative metabolite of G-hesperidin, in spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto rats (WKY) were investigated. Single oral administration of G-hesperidin (10 to 50 mg/kg) induced a dose-dependent reduction in systolic blood pressure (SBP) in SHR, but had no effects in WKY. Intraperitoneal injection of hesperetin (50 mg/kg) into SHR also caused a significant reduction in SBP. The depressor effect was significantly inhibited by a nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester. Moreover, hesperetin (10(-5) M) enhanced endothelium-dependent relaxation induced by acetylcholine, but had no effect on endothelium-independent relaxation induced by sodium nitroprusside in isolated aortas from SHR. These data suggest that the hypotensive effect of hesperetin in SHR is associated with nitric oxide-mediated vasodilation. Therefore, this effect may be involved in the mechanisms by which G-hesperidin lowers blood pressure in hypertension.     

Blood Pressure-Lowering Effect of Wine Lees: Dose-Response Study,Effect of Dealcoholization and Possible Mechanisms of Action

The antihypertensive effect of wine lees (WL) has been previously evidenced. In this study, the antihypertensive properties of different doses of WL were evaluated in spontaneously hypertensive rats (SHR). In addition, the blood pressure (BP)-lowering effect of dried (dealcoholized) WL powder (WLPW) and the mechanisms involved in its functionality were investigated. Furthermore, a possible hypotensive effect of WLPW was discarded in Wistar–Kyoto (WKY) rats. The administration of WL at different doses caused a dose-dependent decrease in BP of SHR up to 5.0 mL/kg bw, exhibiting the maximum decrease at 6 h post-administration. WLPW caused a greater drop in BP than WL, showing an antihypertensive effect higher and more prolonged than the drug Captopril. Moreover, the BP-lowering effect of WLPW was specific to the hypertensive state since an undesirable hypotensive effect in normotensive WKY rats was ruled out. Finally, WLPW improved oxidative stress and increased the activity of the antioxidant endogen system of SHR. These results suggest that WLPW could be used as functional ingredient for foods or nutraceuticals to ameliorate hypertension. Nevertheless, further clinical studies are needed to evaluate its long-term antihypertensive efficiency.     

Effect of casein, casein phosphopeptides and calcium intake on ileal 45Ca disappearance and temporal systolic blood pressure in spontaneously hypertensive rats.

Paracellular 45Ca absorption and temporal systolic blood pressure (SBP) measurements were recorded in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats fed on casein (C) and soya-bean-protein isolate (S) diets, containing 20 (H), 5 (H) and 0.5 (L) g Ca/kg. Similar measurements were also taken in SHR rats only fed on C-M and S-M diets supplemented with 30 g caseinophosphopeptides (CPP)/kg. Absorption of 45Ca from the ileal loop was equivalent in both SHR and WKY animals and largely affected by the level of dietary Ca. In addition, animals fed on C diets exhibited significantly (P < 0.05) greater ileal absorption of 45Ca compared with S-fed animals. This result was attributed to the presence of CPP and a greater (P < 0.05) proportion of soluble 45Ca in the contents of the ileum. Animals fed on S diets supplemented with CPP confirmed this finding. The SBP of SHR rats was higher (P < 0.01) than WKY controls after 9-10 weeks of age. The temporal pattern of observed hypertension was independent of dietary influence in the SHR. The severity of hypertension in SHR rats was affected only by dietary Ca deficiency, and not by Ca supplementation or CPP enhancement of Ca bioavailability. These findings suggest that tryptic digestion products of casein in milk can enhance Ca bioavailability by increasing Ca solubility; however, this action had no effect in reducing hypertension in SHR.     

Acute effects of oral or parenteral aspartame on catecholamine metabolism in various regions of rat brain

Hypertensive (SHR) and nonhypertensive [Wistar-Kyoto (WKY); Sprague-Dawley (SD)] strains of rats received the dipeptide sweetener aspartame (200 mg/kg) or, as a positive control, tyrosine (200 mg/kg) by gavage or parenterally, after a brief (2-h) fast. Two hours later, compared with those of saline controls brain levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylethyleneglycol (MHPG) sulfate were significantly higher in the hypothalamus (WKY), locus coeruleus (SD and SHR) and brain stem (SHR) in tyrosine-treated animals, and in the locus coeruleus (SD) of those given aspartame. Brain norepinephrine levels were also higher, compared with those of saline-treated control rats, in the cerebral cortex (SD and SHR), amygdala (SD) and locus coeruleus (WKY) after tyrosine administration, and in the amygdala (SD) and cerebral cortex (SHR) after aspartame administration. In another study, oral aspartame was found to be at least as effective as the parenterally administered sweetener in raising regional brain levels of tyrosine or MHPG sulfate (i.e., compared with corresponding levels in saline-treated rats). Animals receiving oral aspartame also exhibited higher plasma tyrosine and phenylalanine ratios (i.e., the ratios of their plasma concentrations to the summed concentrations of other large neutral amino acids that compete with them for uptake into the brain), than animals receiving saline.     

Cardiovascular actions of chicken-meat extract in normo- and hypertensive rats.

The cardiovascular actions of a commercial chicken-meat extract known as Brand's Essence of Chicken (Cerebos Pacific Ltd, Singapore; BEC) were investigated in normo- and hypertensive rats. The spontaneously-hypertensive rat (SHR), Wistar Kyoto rat (WKY) and Sprague Dawley rat (SD) were used. The effect of oral feeding of BEC on hypertension, cardiac hypertrophy and arteriosclerosis in these animals was studied. The data showed the following effects of oral feeding of BEC: (1) feeding for 30 d did not affect the blood pressure and heart rate (determined telemetrically) of adult SHR and WKY; (2) feeding for 90 d did not affect the development of hypertension in 1-month-old prehypertensive SHR; (3) feeding for 4 d dose-dependently (0.2--3.2 ml/kg per d) attenuated cardiac hypertrophy in experimentally-induced (coarctation of the abdominal aorta) cardiac hypertrophic SD; (4) feeding to 1-month-old prehypertensive SHR for 11 months did not affect the age-related development of hypertension in this animal; (5) there was significant attenuation of the age-related development of hypertension (determined by tail-cuff plethysmography) in the WKY (P = 0.011) when the animals drank an average of 7.5 ml BEC/kg body weight per d, measured during the last 2 months of the 11-month treatment period; (6) there was chronic, as in the previous treatment, attenuation of the age-related development of cardiac hypertrophy and arteriosclerosis (quantified morphometrically) in the SHR when the animals drank an average of 2.4 ml BEC/kg per d, measured during the last 2 months of the 11-month treatment period. A parallel study using laboratory-prepared chicken-meat and pork extracts showed that the former, but not the latter, attenuated cardiac hypertrophy in experimentally-induced cardiac hypertrophic SD. These findings, showing that chicken-meat extract (both BEC and laboratory prepared) could have anti-cardiac hypertrophic, anti-hypertensive and anti-arteriosclerotic actions, were unexpected and provoking, and would challenge nutritional scientists with an interest in meat consumption and cardiovascular diseases.     

Effects of long-term administration of hesperidin and glucosyl hesperidin to spontaneously hypertensive rats

Hesperidin (HES) is a flavonoid contained in citrus fruit peel. We investigated the effects of long-term administration of HES and its newly developed water soluble analogue, glucosyl hesperidin (GHES), to spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Animals were fed with diets containing HES or GHES (30 mg/d/kg body weight) for 25 wk. While the daily food intake and the body weight of administered rats were not different from those of the non-administered control rats in both SHR and WKY through the experimental period, the blood pressure and heart rate of SHR administered HES or GHES for longer than 15 wk decreased as compared to the control group. The blood pressure and heart rate of WKY were not changed by the long-term administration of HES or GHES. These results suggest that HES and GHES have anti-hypertensive effects on hypertensive animals.     

Changes in arterial blood pressure in hypertensive rats caused by long-term intake of milk fermented by Enterococcus faecalis CECT 5728

We have evaluated the changes in arterial blood pressure caused in spontaneously hypertensive rats (SHR) by long-term intake of an Enterococcus faecalis CECT 5728-fermented milk with significant angiotensin-converting enzyme (ACE)-inhibitory activity. After being weaned, male 3-week-old SHR were randomized into five groups. Until the 20th week of life, rats in each group were given one of the following drinking fluids: tap water (negative control 1), a fermented milk without ACE-inhibitory activity (negative control 2), captopril (100 mg/kg) (positive control), the E. faecalis CECT 5728-fermented milk that had significant ACE-inhibitory activity, or Ca-enriched E. faecalis CECT 5728-fermented milk. Animals in the different groups were then given tap water as drinking fluid from the 20th to 25th week of life. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured weekly in the rats, from the 6th to 25th week of life, by the tail-cuff method. A definite decrease in SBP and DBP could be observed in the rats treated with captopril and also in the rats that received the E. faecalis CECT 5728-fermented milks. The greatest antihypertensive effect was observed when the pharmacological treatment was administered. The effect of the Ca-enriched fermented milk was slightly more accentuated and more constant than the effect of the E. faecalis CECT 5728-fermented milk that had not been enriched in Ca. SBP and DBP increased in the treated SHR when the corresponding antihypertensive treatment was removed. Fermentation of milk with E. faecalis CECT 5728 may therefore be a successful strategy to produce a functional food with antihypertensive activity.     

Blood-pressure-lowering effect of a novel fermented milk containing gamma-aminobutyric acid (GABA) in mild hypertensives

OBJECTIVE: To study the effect of a new fermented milk product containing GABA (FMG) on the blood pressure (BP) of patients with mild hypertension. DESIGN: A randomized, placebo-controlled, single-blind trial. SETTING: The study was carried out at the outpatient clinic of the Cardiovascular Disease Center, Tokyo Metropolitan Police Hospital, Japan. SUBJECTS: The study population comprised 39 mildly hypertensive patients (16 women and 23 men) aged 28-81 y (mean, 54.2 y). INTERVENTIONS: The study consisted of a 12-week period of daily intake of FMG or placebo (weeks 1-12) followed by 2 weeks of no intake (weeks 13 and 14). We measured the peripheral BP and heart rate of seated patients at weeks 0, 2, 4, 8, 12 and 14. Routine blood study and urinalysis were performed before and after the intake. RESULTS: There was a significant decrease of BP within 2 or 4 weeks, and it remained decreased throughout the 12-week intake period. For the FMG recipients, the mean decrease after 12 weeks was 17.4+/-4.3 mmHg in the systolic BP (SBP) and 7.2+/-5.7 mmHg in the diastolic BP (DBP). Both of these values differed statistically from baseline levels (P<0.01), and the SBP of the FMG group differed from the placebo group (P<0.05). Heart rate, body weight, hematological and blood chemistry variables, and urinalysis results (glucosuria and proteinuria) did not vary both groups throughout the study. CONCLUSION: FMG may contribute to lowering BP in mildly hypertensive people.     

Glucosyl hesperidin improves serum cholesterol composition and inhibits hypertrophy in vasculature

Long-term administration of hesperidin (HES) or glucosyl hesperidin (GHES), a water-soluble analogue of HES, brings about an antihypertensive effect on spontaneously hypertensive rats (SHR). In the present study, we investigated the effects of long-term administration of HES and GHES (corresponding to 30 mg/d/kg body weight) on serum lipid concentration and morphology of vasculature. Serum HDL cholesterol increased in both SHR and Wistar-Kyoto rats (WKY) fed a HES- or GHES-containing diet for 25 wk. Simultaneously, GHES administration reduced the vascular diameter and media-intimal cross-sectional area of the abdominal aorta in SHR. These results suggest that HES as well as GHES improves serum cholesterol composition and that GHES inhibits hypertrophy in vasculature as well.     

Effect of a methionine-supplemented diet on the blood pressure of Wistar-Kyoto and spontaneously hypertensive rats

The objectives of the present work were to evaluate the effect of a methionine-supplemented diet as a model of hyperhomocysteinaemia on the systolic blood pressure (BP) and vasomotor functions of aortic rings in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). WKY and SHR rats, randomised into four groups, were fed a normal semisynthetic diet or a methionine (8 g/kg)-supplemented diet for 10 weeks. Systolic BP was measured non-invasively. At the end of the experiment, plasma homocysteine, methionine, cysteine and glutathione levels were determined. Vasoconstriction and vasodilatation of aortic rings were measured. The methionine-supplemented diet induced a significant increase in plasma homocysteine and methionine concentration in both WKY and SHR rats, an increase in plasma cysteine concentrations in WKY rats and an increase in the glutathione concentration in SHR. The systolic BP of WKY rats fed the methionine-supplemented diet increased significantly (P<0.01), whereas systolic BP was reduced in SHR. An enhanced aortic responsiveness to noradrenaline and a decreased relaxation induced by acetylcholine and bradykinin were observed in the WKY rats fed the methionine-enriched diet. In SHR, the bradykinin-induced relaxation was reduced, but the sodium nitroprusside response was increased. In conclusion, a methionine-enriched diet induced a moderate hyperhomocysteinaemia and an elevated systolic BP in WKY rats that was consistent with the observed endothelial dysfunction. In SHR, discrepancies between the decreased systolic BP and the vascular alterations suggest more complex interactions of the methionine-enriched diet on the systolic BP. Further investigations are needed to understand the paradoxical effect of a methionine-rich diet on systolic BP.     

Effects of dietary oleic-rich oils (virgin olive and high-oleic-acid sunflower) on vascular reactivity in Wistar-Kyoto and spontaneously hypertensive rats

The effects of two monounsaturated fatty acid (MUFA)-rich diets, containing virgin olive oil (OO) and high-oleic-acid sunflower oil (HOSO), on development of vascular response from isolated thoracic rat aorta and lipid composition and fatty acid composition were studied and compared with samples from rats fed on a control diet. Dietary MUFA oils were fed for 6 weeks to spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats from 4 weeks of age. The maximum contraction of aortic ring preparations in response to phenylephrine (10(-6) m) was significantly decreased in SHR rats fed with OO (0.81 (sem 0.05) v. 1.18 (sem 0.09) g, and treatment with HOSO did not alter the phenylephrine-induced contractions. The relaxant responses to acetylcholine (10(-5) m) were significantly enhanced (30.03 (sem 0.70) v. 18.47 (sem 0.28) %, in the rings from SHR rats treated with OO, and were more pronounced than in WKY rats In the same way, OO attenuated the dose-response curves induced by phenylephrine (10(-8)-10(-5) m) from SHR rats, accompanied with a slower contraction. These results suggest that only the chronic feeding of OO diet was able to attenuate the vascular response of rat aorta. In addition, an increase in phospholipid content (186.7 (sd 3.2) v. 159.1 (sd 11.3) g/kg, and changes in the fatty acid composition of aorta (mainly a decrease in arachidonic acid) could contribute to improving endothelial function. Therefore, the effects can not be attributed exclusively to the content of MUFA (mainly oleic acid). Other components of OO, such as polyphenols, not present in HOSO, may help to explain the vascular protective effect of OO consumption.     

The role of the sympathetic nervous system in radiation-induced apoptosis in jejunal crypt cells of spontaneously hypertensive rats

To evaluate the effect of the sympathetic nervous system on radiation-induced apoptosis in jejunal crypt cells, apoptosis levels were compared in spontaneously hypertensive rats (SHR), animals which are a genetic hyperfunction model of the sympathetic nervous system, and normotensive Wistar-Kyoto rats (WKY). SHR and WKY were exposed to whole body X-ray irradiation at doses from 0.5 to 2 Gy. The apoptotic index in jejunal crypt cells was significantly greater in SHR than in WKY at each time point after irradiation and at each dose. WKY and SHR were treated with reserpine to induce sympathetic dysfunction, and were subsequently exposed to irradiation. Reserpine administration to SHR or WKY resulted in a significant suppression of apoptosis. p53 accumulation was detected in the jejunum in both WKY and SHR after irradiation by Western blotting analysis. There were no significant differences in the levels of p53 accumulation in irradiated intestine between WKY and SHR. These findings suggested that hyperfunction of the sympathetic nervous system is involved in the mechanism of high susceptibility to radiation-induced apoptosis of the jejunal crypt cells.     

Candesartan治疗对SHR大鼠心肌AngⅡ及其受体表达的影响

目的观察Candesartan早期治疗对SHR大鼠心肌纤维化及心肌AT1、AT2表达的影响,探讨其抗心肌纤维化的机制。方法选取4周龄的雄性自发性高血压大鼠SHR（Spontanous Hypertensive Rat,SHR）及与之年龄性别相配的正常大鼠WKY;动物分组：WKY组、SHR组、Candesartan治疗组（SHR—Can组,给药4周后停药,继续喂养至24周）;尾袖法测定大鼠血压,断头取血,称量全心与左心质量,计算心体比与左室质量指数;放免法测定血浆及心肌AⅡ水平;免疫组化法检测心肌组织中AT1、AT2的表达;Western blotting法测定心肌AT1、AT2的表达水平;天狼星红染色测定心肌胶原指数。结果8周龄后,与SHR组相比,SHR—Can组血压明显下降并持续24周（P〈0．05）;HR-Can组心体比及左室质量指数明显低于SHR组（P〈0．05）;SHR组血浆中AⅡ水平与WKY组相比明显增高（P〈0．01）,SHR—Can组与SHR组相比降低（P〈0．05）;心肌组织AⅡ含量SHR—Can组明显低于SHR组（P〈0．05）。心肌免疫组化染色示：与WKY相比,SHR大鼠AT1、AT2明显增高（P〈0．05）;与SHR相比,SHR-Can组心肌中AT1、AT2明显减少（P〈0．05）。Western blotting结果示：SHR组AT1、AT2表达水平明显高于WKY组（P〈0．05）;SHR—Can组AT1、AT2表达水平明显降低（P〈0．05）。天狼星红染色心肌胶原含量SHR—Can组明显低于SHR组（P〈0．05）。结论Candesartan早期治疗可抑制SHR大鼠高血压的形成与发展,也可抑制SHR心肌纤维化并降低心脏指数,还能降低SHR心肌AT1、AT2的表达,Candesartan抑制心肌纤维化可能与心肌局部AT1、AT2表达水平有关。     

Dietary (n-3) fat and cholesterol alter tissue antioxidant enzymes and susceptibility to oxidation in SHR and WKY rats

Previously, 8% fish oil blend diets, compared to butter and soybean oil blend diets, reduced specific antioxidant enzyme activities and tissue susceptibility to in vitro oxidative stress in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats. Moreover, high cholesterol (5.0 g/kg diet) diets protected against in vitro tissue lipid oxidation. In this study, we hypothesized that 160 g fat/kg diet as blends of (n-6) or (n-3) oils and cholesterol would alter antioxidant enzyme activities and thus increase tissue susceptibility to oxidation. The effects of diet blends of saturated (butter, B), (n-6) (soybean oil, SBO) or (n-3) (menhaden oil, MO) oils with cholesterol (0.5 or 5.0 g/kg) on systolic blood pressure (SBP), plasma lipids, antioxidant enzymes and susceptibility to oxidation were examined in SHR and WKY rats. SBP at 13 wk of age was greater (P < 0.001) in SHR than in WKY rats, but was not affected by diets. Plasma cholesterol and triacylglycerols were decreased (P < 0.001) by MO diets. Hepatic glutathione reductase activities were reduced (P < 0.001) in SBO-fed SHR and enhanced in SBO- and MO-fed WKY rats. Glutathione levels were reduced (P < 0.001) in RBC and enhanced (P < 0.001) in livers of MO-fed rats. Lipid oxidation was enhanced (P < 0.001) in red blood cells (RBC) from SBO groups, and hearts and livers of MO groups. High cholesterol diets reduced (P < or = 0.001) susceptibility to lipid peroxidation in RBC and liver of SHR and WKY rats. Greater amounts of dietary (n-3) fat enhance tissue susceptibility to oxidation, which can be modulated by increased dietary cholesterol in SHR and WKY rats.     

不同品系大鼠开场自发活动水平的研究

目的 以常用的注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)模型自发性高血压大鼠(spontaneously hypertensive rats,SHR)为观察对象,观察其与注意缺陷多动障碍临床特征在行为学上的相似性。方法 SHR、SD(Sprague Dawley rats,SD)、WKY(Wistar Kyoto rats,WKY)大鼠各10只,利用开场实验观察记录大鼠穿越的格子数、直立次数、理毛次数、粪便颗粒数。结果 反映大鼠活动能力的穿越格数及直立次数,SHR大鼠均明显较对照组WKY、SD大鼠增多,差异有高度统计学意义(P<0.01);而表现情绪紧张程度的理毛次数和排便粒数,SHR大鼠与对照组WKY、SD大鼠的差异无统计学意义(P>0.05)。结论 SHR大鼠的多动性明显高于SD、WKY大鼠,能很好的再现注意缺陷多动障碍的多动行为学特征,是比较理想的注意缺陷多动障碍的动物模型。     

嗜热链球菌grx02发酵乳对大鼠酒精性肝损伤保护作用的实验研究

目的研究嗜热链球菌grx02对酒精性肝损伤大鼠肝细胞线粒体功能的保护作用,探讨其可能的作用机制。方法以56%酒精灌胃,复制大鼠酒精性肝损伤模型。Wistar大鼠随机分为对照组、模型组、东宝肝泰干预组、样品组、阳性对照组,每组10只。grx02发酵乳(高、中、低剂量)分别灌胃含乳酸菌数为108、107、106cfu/ml的脱脂乳发酵液14 ml/kg bw,连续6w。末次灌胃前晚禁食不禁水,灌胃1h后,对照组灌胃蒸馏水,其它各组灌胃50%酒精14ml/kg bw。12h后处死大鼠,检测血清中的谷氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、和甘油三酯(TG);提取肝细胞线粒体,测定丙二醛(MDA)含量,超氧化物歧化酶(SOD)、Na+-K+-ATPase,Ca2+-ATPase活力。结果与模型组比较,嗜热链球菌grx02可降低血清ALT、AST、TG水平,提高线粒体Na+-K+-ATPase,Ca2+-ATPase酶活性(P<0.05);且高剂量下各项指标优于其他组。结论嗜热链球菌grx02可改善酒精诱导急性肝损伤模型大鼠的肝功能,其可明显抑制酒精引发的肝细胞线粒体脂质过氧化反应,减轻自由基对线粒体的氧化损伤,并且它还可增强线粒体Na+-K+-ATPase、Ca2+-ATPase等ATP依赖酶的活性。     

Dietary (n-3) polyunsaturated fatty acids exert antihypertensive effects by modulating calcium signaling in T cells of rats

After 10 wk of feeding an experimental diet enriched with (n-3) polyunsaturated fatty acids (PUFA), i.e., eicosapentaenoic acid [EPA, 20:5(n-3)] and [DHA, 22:6(n-3)] (EPAX), blood pressure in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto (WKY) rats was reduced relative to rats fed an unsupplemented control diet. Concanavalin A-stimulated T-cell proliferation was diminished in both strains of rats fed the PUFA/EPAX diet. The experimental diet lowered secretion of interleukin-2 in SHR, but not in WKY rats compared with rats fed the control diet. To determine whether there was a defect in calcium homeostasis in T cells during hypertension, we employed the following agents: caffeine, which recruits calcium from the cytosolic Ca(2+)-induced Ca(2+)-release pool; ionomycin, which at low concentrations opens calcium channels; and thapsigargin (TG), which mobilizes [Ca(2+)]i from the endoplasmic reticulum (ER) pool. Caffeine-induced increases in [Ca(2+)]i were not modified by the PUFA/EPAX diet. The ionomycin-induced increases in [Ca(2+)]i in T cells from SHR were greater than in those from WKY rats; consumption of the PUFA/EPAX diet did not modify Ca(2+) influx in cells of either strain. The TG-induced increases in [Ca(2+)]i in T cells from SHR were greater than those in cells from WKY rats. Interestingly, consumption of the experimental diet reduced TG-evoked increases in [Ca(2+)]i in T cells from SHR and increased those in T cells from WKY rats, indicating that the PUFA/EPAX diet could reverse the calcium mobilization from the ER pool in T cells. These results suggest that (n-3) PUFA exert antihypertensive effects and modulate T-cell calcium signaling during hypertension in rats.     

The effect of nutrient profiles of the Dietary Approaches to Stop Hypertension (DASH) diets on blood pressure and bone metabolism and composition in normotensive and hypertensive rats

Hypertension has been associated with abnormalities of Ca and bone metabolism. Consequently, dietary strategies aimed at reducing blood pressure may also benefit bone health; however, this issue has received little attention. Therefore, the objective of the present study was to investigate the effect of two antihypertensive-type diets on blood pressure and bone metabolism and composition in normotensive (Wistar-Kyoto NHsd, WKY) and hypertensive (spontaneously hypertensive NHsd, SHR) rats. Thirty WKY and thirty SHR male rats, 14 weeks old, were separately randomized by weight into three groups of ten rats each. One group from each strain was given a control diet while the other two groups were fed two anti-hypertensive (high fruit and vegetable (F/V) and high fruit and vegetable and low-fat dairy produce (combination)) diets for 8 weeks. SHR rats were significantly (P<0.01) heavier than WKY rats. Blood pressure and femoral length, width, dry weight, ash, Ca, Mg, P and bone mineral mass were significantly (P<0.0001) greater in SHR than WKY rats, but were unaffected by diet, irrespective of strain. While markers of bone formation (serum osteocalcin) and bone resorption (urinary pyridinoline and deoxypyridinoline) were similar in both strains, these markers were significantly (P<0.05) lower (28-31, 16-23, 31-33 % respectively) in the SHR rats fed the combination diet relative to those fed the control and F/V diets. Bone turnover in WKY rats was unaffected by diet. In conclusion, these findings suggest that the combination diet may benefit bone metabolism in hypertensive animals. However, as blood pressure was unaffected by this diet, the mechanism by which it reduced bone turnover requires further investigation.     

A quercetin supplemented diet does not prevent cardiovascular complications in spontaneously hypertensive rats

Diets high in quercetin may decrease the risk of developing cardiovascular disease. We tested whether quercetin delays or reduces the severity of hypertension, vascular dysfunction, or cardiac hypertrophy in the spontaneously hypertensive rat (SHR). Normotensive, 5-wk-old SHR consumed standard (n = 18) or quercetin-supplemented diet (1.5 g quercetin/kg diet, n = 22, SHR-Q) for 5 or 11 wk. Wistar Kyoto rats (WKY, n = 19), fed a standard diet, served as controls. At 16 wk, plasma quercetin, measured by HPLC, was 2.09 +/- 0.33 micromol/L in SHR-Q and below assay detection limits in SHR and WKY rats. At 10 and 16 wk of age, arterial blood pressure and heart weight:body weight were not different between SHR and SHR-Q. At 16 wk, cardiac function (echocardiography), vascular morphology (hematoxylin and eosin staining of aortae), and resistance and conductance vessel reactivity (wire myography) was unchanged in SHR vs. SHR-Q. Thus, a quercetin-supplemented diet does not delay the onset or lessen the severity of cardiovascular complications that develop in SHR. These findings contrast with previous reports of cardiovascular protection when quercetin was delivered via oral gavage. To determine whether the efficacy of quercetin depends on its method of delivery, 15-wk-old SHR were given quercetin (10 mg/kg) once daily via oral gavage for 4 consecutive days. Arterial blood pressure (mm Hg) was lower in gavaged SHR (148 +/- 5) than in SHR-Q (162 +/- 2, P < 0.02) and SHR (168 +/- 3, P < 0.001). These data suggest that mode of delivery is a critical determinant in whether quercetin provides cardiovascular benefits.     

Depressed prostanoid-induced contractility of the gut in spontaneously hypertensive rats (SHR) is not affected by the level of dietary fat

Dietary saturated fat (SF) has adverse effects on cardiac and vascular smooth muscle (VSM) contractility. Furthermore, VSM of spontaneously hypertensive rats (SHR) is overreactive to various biological stimuli. The aim of this study was to investigate the effects of increasing dietary fat as lard on gut contractility in SHR. Control Wistar-Kyoto (WKY) rats and SHR (13 wk old) were fed for 12 wk a diet containing 3% sunflower oil [low fat (LF), 3% total fat] or diets supplemented with 7% lard [medium fat (MF), 10% total fat] or 27% lard [high fat (HF), 30% total fat]. For ileal and colonic tissues (WKY and SHR), there was a lower total phospholipid PUFA (n-6)/(n-3) ratio with increased dietary SF (P < 0.003). For WKY, increasing SF led to lower levels of the major SCFA and lower total SCFA levels in cecal digesta (P < 0.01). This trend was evident in SHR but significant only for butyrate (P < 0.01). Contractility responses were unaltered in ileum. In colon, there was a change of sensitivity (50% effective concentration) to angiotensin II in WKY (P < 0.05) due to increased SF and a change of sensitivity to prostaglandin (PG)E(2) and carbachol in SHR (P < 0.05). When the 3 dietary groups were combined, there was lower sensitivity (P < 0.01) and lower maximal contraction (P < 0.05) in ileum and lower maximal contraction in colon of SHR in response to PGF(2alpha) (P < 0.05) and PGE(2) (P < 0.01) compared with WKY. Unlike (n-3) PUFA, dietary SF had little overall effect on gut contractility. However, this is the first report of a defect in PG responsiveness from gut tissue from hypertensive rats.