The effect of diets adequate and deficient in calcium on blood pressures and the activities of intestinal and kidney plasma membrane enzymes in normotensive and spontaneously hypertensive rats

Basolateral and brush-border membranes were prepared from the intestines and kidneys of spontaneously hypertensive (SHR) and normotensive (WKY) rats fed on a calcium-adequate diet and assayed for their enzyme activities. In intestinal basolateral membranes the activities of Na+ K(+)-ATPase (EC 3.6.1.37) Ca2(+)-ATPase (EC 3.6.1.38) and alkaline phosphatase (EC 3.1.3.1) were lower in SHR rats when compared with WKY rats, whilst 5'-nucleotidase (EC 3.1.3.5) (a marker for basolateral membranes) was unaffected. In kidney basolateral membranes all enzymes were similar in activity in SHR and WKY rats. In intestinal brush-border membranes the activities of Ca2(+)-ATPase and alkaline phosphatase were lower in SHR rats when compared with WKY rats, whilst microvillus aminopeptidase (EC 3.4.11.2) (a marker for brush-border membranes) was unaffected. In kidney brush-border membranes all enzymes were similar in activity in SHR and WKY rats. The blood pressures of the SHR rats were considerably higher than those of the WKY rats. When SHR rats were fed on a Ca-deficient diet the activities of Na+K(+)-ATPase, Ca2(+)-ATPase and alkaline phosphatase in basolateral membranes and Ca2(+)-ATPase and alkaline phosphatase in brush-border membranes were all increased in the intestine when compared with SHR rats fed on a Ca-adequate diet. The equivalent enzymes in the kidneys of SHR rats, and the intestines and kidneys of WKY rats, were not affected by altering the Ca in the diet. The blood pressures of SHR rats fed on a Ca-deficient diet were higher than in those fed on a Ca-adequate diet. Blood pressures of WKY rats were not affected by altering the diet in this way. The results indicate that the absorption of Ca by active mechanisms may be reduced in SHR rats compared with WKY rats. Changing the level of Ca in the diet modified both blood pressure and the activities of enzymes which catalyse active Ca transport. The implications of these results to the aetiology, and possible nutritional treatment, of essential hypertension are discussed.     

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.     

Effects of deep-frying oil on blood pressure and oxidative stress in spontaneously hypertensive and normotensive rats

ObjectiveIngestion of deep-frying oil has been reported to cause physiologic and histologic changes in experimental animals' tissue, increase the oxidative stress, and possibly lead to death. The purpose of this study was to investigate the effect of deep-frying oil on oxidative stress and blood pressure in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats.MethodsDeep-frying oil was prepared by frying fresh soybean oil at 180 ± 5°C for 8 h each day, for 4 consecutive days. Male SHR and WKY rats were fed diets containing 15% fresh soybean oil or deep-frying oil (DO) for 10 wk.ResultsRats ingesting the DO diet had lower feed efficiency and higher relative liver and kidney weights but deep frying had no significant influence on blood pressure in WKY or SHR rats. The DO diet had no effect on plasma renin activity, aldosterone content, or tissue angiotension-I–converting enzyme activity. WKY rats fed the DO diet showed significantly increased urinary thromboxane B₂ and 8-iso-prostaglandin F_2α excretion, but not urinary 6-keto-prostaglandin F_1α excretion. Diets containing deep-frying oil resulted in increased plasma thiobarbituric acid-reactive substances and nitric oxide contents and decreased plasma total antioxidant capacity in SHR and WKY rats.ConclusionThe ingestion of deep-frying oil seemed not to influence blood pressure or its related parameters, but altered eicosanoid metabolism and elevated oxidative stress in SHR and WKY rats.     

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.     

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.     

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.     

Nutrient interactions in hypertension

Normotensive Wistar rats (n=84) and spontaneously hypertensive rats (SHR; n=90) and their Wistar Kyoto (WKY; n=24) controls were fed 17% fat diets for four months. Three dietary fats-butter, and two margarines which represented 1:1 and 3:1 ratios of polyunsaturated to saturated fatty acids were used in three different diets; 1) a low sodium diet containing no NaCl in which the carbohydrate component was a 50:50 mixture of cornstarch and sucrose; 2) a diet containing 3.5% added NaCl and a 50:50 mixture of cornstarch and sucrose; and 3) a diet containing 3.5% NaCl and 100% sucrose as the carbohydrate component. After four months on the experimental diets, Wistar rats fed butter or margarine 1:1 in Diet 2 developed a significant elevation of blood pressure as compared with Diet 1, but rats fed margarine 3:1 did not develop hypertension. All SHR developed hypertension. On Diet 1 which had no NaCl, the blood pressure of rats fed margarine 3:1 were significantly higher than those fed butter. On Diet 2, which had 3.5% added NaCl, the blood pressures of all three fat groups rose to the same level. On Diet 3 which contained 3.5% NaCl and 100% sucrose as carbohydrate, both the margarine 3:1 and margarine 1:1 fat groups showed a further increase in blood pressure as compared with Diet 2, but the increase in the group fed butter was not significant. None of the increases in blood pressure observed could be attributed to increased weight gain. Salt, sucrose and fat have all been implicated previously in hypertension. These results show that there is a definite interaction among these dietary components; depending on the composition of the diet, hypertension may be aggravated or attenuated.     

Effects of kimchi supplementation on blood pressure and cardiac hypertrophy with varying sodium content in spontaneously hypertensive rats

We tested the effects of dietary intake of freeze-dried Korean traditional fermented cabbage (generally known as kimchi) with varying amounts of sodium on blood pressure and cardiac hypertrophy in spontaneously hypertensive rats (SHRs). Wistar-Kyoto rats (WKY), as a control group, received a regular AIN-76 diet, and the SHRs were divided into four groups. The SHR group was fed a regular diet without kimchi supplementation, the SHR-L group was fed the regular diet supplemented with low sodium kimchi containing 1.4% salt by wet weight, which was provided in a freeze-dried form, the SHR-M group was supplemented with medium levels of sodium kimchi containing 2.4% salt, and the SHR-H group was supplemented with high sodium kimchi containing 3.0% salt. Blood pressure was measured over 6 weeks, and cardiac hypertrophy was examined by measuring heart and left ventricle weights and cardiac histology. SHRs showed higher blood pressure compared to that in WKY rats, which was further elevated by consuming high sodium containing kimchi but was not influenced by supplementing with low sodium kimchi. None of the SHR groups showed significant differences in cardiac and left ventricular mass or cardiomyocyte size. Levels of serum biochemical parameters, including blood urea nitrogen, creatinine, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, sodium, and potassium were not different among the groups. Elevations in serum levels of aldosterone in SHR rats decreased in the low sodium kimchi group. These results suggest that consuming low sodium kimchi may not adversely affect blood pressure and cardiac function even under a hypertensive condition.     

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.     

A polyunsaturated fatty acid diet lowers blood pressure and improves antioxidant status in spontaneously hypertensive rats

gamma-Linolenic acid [GLA, 18:3(n-6)], eicosapentaenoic acid [EPA, 20:5(n-3)] and docosahexaenoic acid [DHA, 22:6(n-3)] have been reported to prevent cardiovascular diseases. However, they are highly unsaturated and therefore more sensitive to oxidation damage. We investigated the effects of a diet rich in these polyunsaturated fatty acids (PUFA) on blood pressure, plasma and lipoprotein lipid concentrations, total antioxidant status, lipid peroxidation and platelet function in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Five-week-old SHR and WKY rats were fed for 10 wk either a diet containing Isio 4 oil or a diet rich in GLA, EPA and DHA (5.65, 6.39 and 4.94 g/kg dry diet, respectively). The total antioxidant status was assayed by monitoring the rate of free radical-induced hemolysis. VLDL-LDL sensitivity to copper-induced lipid peroxidation was determined as the production of thiobarbituric acid reactive substances. After dietary PUFA supplementation, a significant decrease in blood pressure of SHR rats (-20 mm Hg) was observed and the total antioxidant status was enhanced. VLDL-LDL resistance to copper-induced peroxidation was increased in both strains. The PUFA supplementation did not change platelet maximum aggregation in SHR rats, but it decreased the aggregation speed. In hypertensive rats, GLA + EPA + DHA supplementation lowers blood pressure, enhances total anti-oxidant status and resistance to lipid peroxidation, diminishes platelet aggregation speed and lowers plasma lipid concentrations. Thus, it enhances protection against cardiovascular diseases. Therefore, nutritional recommendations for cardiovascular disease prevention should take into account the pharmacologic properties of GLA, EPA and DHA.     

Effect of dietary level of Vitamin E on the immune system of the spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rat

Spontaneously hypertensive rats (SHR) had depressed splenic mitogen responses as well as lower splenic vitamin E when compared to normotensive Wistar Kyoto strain (WKY) rats fed a stock diet. Both strains had depressed T- and B-cell splenic mitogen responses after 17 weeks on a semipurified, vitamin E-deficient diet when compared to animals fed either stock or dl-alpha-tocopheryl acetate-supplemented semipurified diet. In addition, SHR fed the vitamin E-supplemented diet had enhanced thymocyte rosetting compared to those fed the vitamin E-deficient diet. In contrast, the dietary vitamin E level did not affect the thymocyte rosetting in WKY rats.     

Effect of a gamma-aminobutyric acid-enriched dairy product on the blood pressure of spontaneously hypertensive and normotensive Wistar-Kyoto rats

We investigated the blood-pressure-lowering effects of gamma-aminobutyric acid (GABA) and a GABA-enriched fermented milk product (FMG) by low-dose oral administration to spontaneously hypertensive (SHR/Izm) and normotensive Wistar-Kyoto (WKY/Izm) rats. FMG was a non-fat fermented milk product produced by lactic acid bacteria, and the GABA contained in FMG was made from the protein of the milk during fermentation. A single oral dose of GABA or FMG (5 ml/kg; 0.5 mg GABA/kg) significantly (P<0.05) decreased the blood pressure of SHR/Izm from 4 to 8 h after administration, but did not increase that of WKY/Izm rats. The hypotensive activity of GABA was dose-dependent from 0.05 to 5.00 mg/kg in SHR/Izm. During the chronic administration of experimental diets to SHR/Izm, a significantly slower increase in blood pressure with respect to the control group was observed at 1 or 2 weeks after the start of feeding with the GABA or FMG diet respectively (P<0.05) and this difference was maintained throughout the period of feeding. The time profile of blood-pressure change due to administration of FMG was similar to that of GABA. FMG did not inhibit angiotensin 1-converting enzyme. Furthermore, an FMG peptide-containing fraction from reverse-phase chromatography lacked a hypotensive effect in SHR/Izm rats. The present results suggest that low-dose oral GABA has a hypotensive effect in SHR/Izm and that the hypotensive effect of FMG is due to GABA.     

Acanthopanax divaricatus var. chiisanensis reduces blood pressure via the endothelial nitric oxide synthase pathway in the spontaneously hypertensive rat model

In this study, we investigated the antihypertensive effects of Acanthopanax divaricatus var. chiisanensis extract (AE) and its active compound, acanthoside D (AD), on arterial blood pressure (BP) in vivo and endothelial function in vitro. We hypothesized that AE has antihypertensive effects, which is attributed to enhancement of endothelial function via the improvement of nitric oxide synthesis or the angiotensin II (Ang II) response. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) were randomly divided into 7 groups and then fed the following diets for 14 weeks: WKY fed a normal diet (WN); SHR fed a normal diet (SN); SHR fed a high-cholesterol (HC) diet (SH); SHR fed a HC diet with AE of 150, 300, 600 mg/kg body weight (SH-L, SH-M, SH-H); and SHR fed an HC diet with AD of 600 μg/kg body weight (SH-D). Blood pressure was significantly reduced in the SH-H compared with the SH from week 10 until week 14; BP was also significantly decreased in the SHR fed a HC diet with AE of 300 at week 14. Aortic wall thickness showed a tendency to decrease by AE and AD treatment. The SH-H showed increased endothelial nitric oxide synthase (eNOS) expression in the intima and media, compared with the SH. Furthermore, a significant increase in intracellular nitric oxide production was induced by AE and AD treatment in human umbilical vein endothelial cells. A significant increase of phospho-eNOS was found with a high dose of AE in human umbilical vein endothelial cells but not with AD. These results suggest that AE can regulate BP and improve endothelial function via eNOS-dependent vasodilation.     

Effects of dietary fish oil or pectin on blood pressure and lipid metabolism in the DOCA-salt hypertensive rat

This study investigated the effects of diets containing fish oil or pectin on blood pressure and lipid metabolism in the deoxycorticosterone acetate (DOCA)-salt hypertensive rat. Three groups (8 rats/group) of unilaterally nephrectomized rats were fed for 21 d one of three purified diets: a) 8% fish oil + 2% safflower oil + 5% alpha cellulose (fish oil diet), b) 10% safflower oil + 5% pectin (pectin diet), or c) 10% safflower oil + 5% alpha cellulose (control diet). Each of the diets contained 6% NaCl and all rats received DOCA (30 mg/kg body wt, subcutaneously) twice weekly. Systolic blood pressure of rats fed fish oil was significantly lower (P less than 0.05) than that of rats fed the control diet; there was no significant difference between the pectin and control groups. Plasma renin activity and net sodium and potassium balances were similar among the three groups. Plasma total cholesterol, LDL cholesterol and HDL cholesterol were significantly lower (P less than 0.05) in the group fed the fish oil diet than in the group fed the control diet. Total, LDL and HDL cholesterol did not differ between rats fed the pectin and rats fed the control diet. Plasma triglyceride concentration did not differ among the three groups. Thus, dietary fish oil attenuated the development of DOCA-salt hypertension, unrelated to alterations of net sodium balance. Fish oil feeding also lowered total, LDL and HDL cholesterol, but did not alter the HDL/LDL ratio. In contrast, dietary pectin exerted no effect on blood pressure or lipid metabolism.     

Effects of voluntary running exercise on blood pressure and renin-angiotensin system in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats

The effect of a voluntary running exercise on blood pressure and renin-angiotensin system (RAS) was studied in male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). SHR and WKY were assigned to either voluntary running exercise or sedentary control groups at 5 wk of age. The systolic blood pressure in the exercised group for both strains of rats was significantly lower than in the sedentary control group. The plasma renin activity (PRA) and plasma renin concentration (PRC) were significantly lower in voluntary running exercised SHR than in sedentary SHR, whereas the same exercise did not result in a lower PRA and PRC in WKY. These results suggested that the blood pressure lowering effect of voluntary running exercise is related to the suppression of RAS in SHR.     

氯沙坦对自发性高血压大鼠肾组织钙离子浓度的影响及与肾小动脉重建的关系研究

目的探讨钙超负荷与高血压。肾小动脉重建的关系及氯沙坦（Losartan）的治疗作用。方法正常血压Wistar-Kyoto（WKY）大鼠和同种的16周龄自发高血压大鼠（spontaneously hyperten—siverat,SHR）大鼠随机分为WKY对照组、SHR对照组、高剂量losartan组（SHR＋HL）、低剂量losar—tan组（SHR＋LL）。每组6只动物。给予正常饮食,饲养至24周。losartan溶于10ml生理盐水中灌胃,余组等量生理盐水灌胃。测量尾动脉血压、肾组织钙离子浓度、肾小动脉内羟脯氨酸含量并观察肾脏病理测量肾人球小动脉中膜厚度、血管内径及中膜厚度与内径比值（MT／LR）。结果SHR组肾组织钙离子浓度[（18．42±2．34）μ mol／g]、肾小动脉内羟脯氨酸含量[（8．26±2．02）mg／g]均大于WKY组[（11．83±1．98）μmoL／g,（5．16±0．98）mg／g]（t=3．116,3．258,P〈0．05）,但两治疗组均有所降低,小于SHR组（t：2．946,P〈0．05）。SHR组肾内小动脉的壁厚[（5．25±1．13）μm]、壁厚内径比[（9．57±1．78）％]均大于WKY组相应比值[（4．03±0．16）斗m,（7．12±1．35）％]（t=2．836,3．425,P〈0．05）,但两治疗组壁厚内径比[（7．64±1．29）％,（7．85±1．32）％]小于SHR组（t=3．512,3．648,P〈0．05）。结论losartan可以通过抑制细胞内钙超负荷、降低纤维化程度来改善肾小动脉的血管阻力,对高血压大鼠的。肾小动脉重建有逆转作用。     

The effect of bovine whey protein on ectopic bone formation in young growing rats

The beneficial effect of bovine whey protein (WP) on bone metabolism has been shown in adult human subjects and ovariectomised rats. However, its effect on bone formation in earlier life, particularly during periods of bone mineral accrual, has not been investigated. Twenty-one male rats (4 weeks old, Wistar strain) were randomised by weight into three groups of seven rats each and fed ad libitum on a semi-purified low-Ca diet (3.0 g Ca/kg diet) containing 0 (control), 10 (diet WP1) or 20 (diet WP2) g bovine WP/kg for 47 d. On day 34 of the dietary intervention, all rats had two gelatine capsules containing demineralised bone powder implanted subcutaneously in the thorax region (a well-established in vivo model of ectopic bone formation). At 14 d after implantation, alkaline phosphatase activity (reflective of bone formation) in the bone implants from animals fed WP1 and -2 diets was almost 2-fold (P<0.01) that of control animals. Insulin-like growth factor (IGF)-I mRNA levels were about 3-fold (P<0.05) higher in implants from animals fed the WP diets compared with those from control animals. Serum- and urine-based biomarkers of bone metabolism and bone mineral composition in intact femora were unaffected by WP supplementation. In conclusion, the present findings suggest that bovine WP can enhance the rate of ectopic bone formation in young growing rats fed a Ca-restricted diet. This effect may be mediated by an increased synthesis of IGF-I in growing bone. The effect of WP on bone formation warrants 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.     

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.     

Development of hypertension in spontaneously hypertensive rats fed L-tyrosine-supplemented diets

The blood pressure of spontaneously hypertensive rats (SHR) was measured by tail-plethysmography. Feeding SHR a diet supplemented with 0.6 g% L-tyrosine, for 15 weeks after weaning, resulted in a slower increase of blood pressure than in rats fed the control diet (no tyrosine added). The blood pressure stabilized, after about 8 weeks, at values lower by about 10 mm Hg than in the control SHR group. Diets with a higher content of free L-tyrosine (1.2 or 2.4 g%) produced no greater hypotensive effects, despite the fact that the plasma level of the amino acid, at the time of blood pressure measurements, was related to the tyrosine content of the diet. In addition, providing 2.4 g% free L-tyrosine to the diet of SHR with established hypertension, produced within a few days a decrease of blood pressure similar to the one recorded in rats fed the tyrosine-supplemented diet during the whole period of development of hypertension. A maximal effect of L-tyrosine, in decreasing the blood pressure of SHR, is thus obtained at relatively low concentrations of the amino acid in the diet, and after a short period of consumption. However, this effect is rather small, and rapidly reversed upon removing free L-tyrosine from the diet.