Studies on stroke-prone spontaneously hypertensive rats (SHRSP) fed a high-fat and high-cholesterol diet--effect of taurine on serum lipoprotein metabolism in hypercholesterolemic rats

It is well known that taurine, a final metabolite of sulfur-containing amino acids, plays an important role in bile acid metabolism and that it also has a moderately hypotensive effect. Moreover, it has recently been revealed that taurine shows a hypocholesterolemic effect in animals with experimentally induced hypercholesterolemia. However, the hypocholesterolemic mechanism remains unresolved. Stroke-prone spontaneously hypertensive rats (SHRSP) easily develop hypercholesterolemia when fed a high-fat and high-cholesterol diet (HFC diet). In our previous paper, we reported changes in the concentrations and distributions of serum lipoproteins and apolipoproteins in hypercholesterolemic SHRSP and Kyo: Wistar rats (WKY) induced by HFC feeding. In this paper, to elucidate the mechanism of the hypocholesterolemic effect of taurine, we investigated the effects of taurine on concentrations and distributions of serum lipoproteins and apolipoproteins in hypercholesterolemic SHRSP and WKY induced by HFC feeding. The results obtained were as follows: 1) The hypocholesterolemic effect of taurine in hypercholesterolemic SHRSP was remarkable in comparison with that in hypercholesterolemic WKY. 2) The hypocholesterolemic effect of taurine was mainly due to a marked suppression of extreme elevations of cholesterol contents in the VLDL and IDL fractions of both strains. This was associated with a decrease in the elevated contents of apo B and apo E which are major components of VLDL and IDL. This suppressive effect was more obvious in SHRSP than in WKY, which explains the greater hypocholesterolemic effect of taurine in SHRSP. It could be that, as a result of taurine administration, the catabolism of cholesterol to bile acid in the liver is accelerated, followed by a decrease of the hepatic cholesterol pool, resulting in a suppression of the synthesis and/or secretion of VLDL (beta-VLDL) in the liver. 3) The hypocholesterolemic effect of taurine was also observed in the LDL fractions of both strains, but the effect was not as strong as that observed in the VLDL and IDL fractions. This effect might be attributable to suppression of the synthesis and/or secretion of LDL in the liver and a decrease in the elevated content of apo E HDL (HDLc) which spans two density fractions (the LDL and HDL fractions). 4) In HDL fractions of both strains, the decreased content of apo E HDL (HDL1 and HDLc) was even lower, whereas the decreased apo A-I content in the HDL fraction of SHRSP was significantly restored and the cholesterol level was slightly elevated.(ABSTRACT TRUNCATED AT 400 WORDS)     

Studies on stroke-prone spontaneously hypertensive rats (SHRSP) fed a high-fat and high-cholesterol diet--changes in serum concentrations and distributions of apolipoproteins A-I, A-IV and E

The effects of a high-fat and high-cholesterol diet (HFC diet) on serum lipoproteins and apolipoproteins were studied in stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Kyo: Wistar rats (WKY). In particular, the changes in serum concentrations and distributions among lipoprotein fractions of apolipoproteins A-I, A-IV and E (apo A-I, A-IV and E) were investigated in detail. These apolipoproteins are the main protein constituents of high density lipoprotein (HDL) which is considered to be an anti-atherogenic factor and accounts for a large part of the serum lipoproteins in the rat. Serum lipoprotein fractions were isolated by stepwise density-gradient ultracentrifugation. The alterations in lipoprotein fractions and apolipoproteins in lipoprotein fractions were roughly estimated by native gradient polyacrylamide gel electrophoresis and sodium dodecyl sulfate (SDS)-gradient polyacrylamide gel electrophoresis. Next, the concentrations of apo A-I, A-IV and E in serum, serum lipoprotein fractions and serum lipoprotein-free fraction were measured by rocket immunoelectrophoresis according to the method of Laurell as modified by us. Cholesterol was enzymatically determined by a commercially available kit. The results obtained were as follows: 1) A remarkable increase in the very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) fractions was observed in WKY and SHRSP. This was associated with a remarkable increase in the cholesterol and apo B contents and with a significant increase in the apo E content. These changes in the VLDL and IDL fractions were more drastic in SHRSP than in WKY, which suggests the promotive effect of hypertension in SHRSP on the production of VLDL and IDL fractions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of repeated phase shifts in light-dark cycles on lipid metabolism in stroke-prone spontaneously hypertensive rats (SHRSP)]

In the present paper, we employed the stroke-prone spontaneously hypertensive rat (SHRSP) as an animal model and the Kyo: Wistar rat (WKY) as a control, and studied on the effect of repeated phase shifts in light-dark cycles on lipid metabolism. First, we investigated diurnal rhythms of the lipid metabolism in SHRSP and WKY. In both strains, the activities of lipoprotein lipase (LPL) and hepatic microsomal cholesterol 7 alpha-hydroxylase in the dark period were significantly higher than those in the light period. In addition, in SHRSP, the serum apoA-IV level in the dark period was also higher than that in the light period. Next, we repeated the phase shifts in light-dark cycles twice a week with elongation of the light period for 4 weeks. LPL activity in the light period increased in response to the repeated phase shifts in both strains. This might be a defensive reaction to maintain homeostasis in the lipid metabolism in addition to energy production. Moreover, we performed repeated phase shifts in rats fed a high-fat and high-cholesterol diet containing 0.1% propylthiouracil to elucidate the effect on the development of hypercholesterolemia. The repeated phase shifts increased the levels of atherogenic lipoproteins and the atherogenic index (apoB/apoA-I). In particular, the effect was more marked in SHRSP. This deleterious effect could be due to the overproduction of very low density lipoprotein (VLDL, beta-VLDL) in the liver.     

Effect of milk protein and fat intake on blood pressure and the incidence of cerebrovascular diseases in stroke-prone spontaneously hypertensive rats (SHRSP)

The intake of two milk protein-rich diets containing casein and whey protein attenuated the development of severe hypertension in stroke-prone spontaneously hypertensive rats (SHRSP), and extended their life span in comparison with SHRSP on a regular stock diet. Milk fat-rich diet intake reduced the incidence of cerebrovascular disease in SHRSP without a significant fall in blood pressure. These results suggest that certain milk components have a preventive effect on hypertension and cerebrovascular disease in SHRSP.     

Prophylactic effects of diets on the development of cerebrovascular lesions in stroke- prone spontaneously hypertensive rats (SHRSP)--effects of a fish-protein diet and alterations of lipoprotein metabolism

It is generally accepted that a high-protein diet prevents the development of cerebrovascular lesions and improves the survival rate in studies using stroke-prone spontaneously hypertensive rats (SHRSP). Moreover, it is well documented that the preventive effect is largely due to attenuation of the development of severe hypertension. However, in addition to the reduction of blood pressure, there must be some other mechanisms which are nutritionally effective. In order to elucidate nutritionally effective mechanisms, we investigated the prophylactic effect of a protein diet (the K diet) on the development of cerebrovascular lesions in SHRSP. The diet was composed of dried bonito protein as the protein source and contained the same amount of protein as the control diet (the Funabashi SP diet). Experimental groups were maintained on the K diet from 5 (ca. 130 mmHg), 8 (ca. 200 mmHg) or 10 (ca. 230 mmHg) weeks of age and the control group was maintained on the Funabashi SP diet, with free access to the diet and to drinking water. In the experimental groups administered the K diet from 5 or 8 weeks of age, the development of hypertension was attenuated, there was a reduction of the incidence of cerebrovascular lesions and elongation of the life-span was observed. On the other hand, in the experimental group administered the K diet from 10 weeks of age, a reduction of the incidence of cerebrovascular lesions and an elongation of the life-span were observed without the reduction of blood pressure. Taking the above results into account, we investigated the serum lipid metabolism, which might be affected by the administration of the K diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential effects of dietary canola and soybean oil intake on oxidative stress in stroke-prone spontaneously hypertensive rats

Background

Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine involved in inflammation and pathogenesis of atherosclerosis. There is scant information on the relation between variations within the TGF-β1 gene polymorphisms and risks of ischemic cerebrovascular diseases. Therefore, this case-controlled study was carried out to investigate the possible association of the TGF-β1 gene C-509T and T869C polymorphisms, and their combined genotypes with the risk of atherosclerotic cerebral infarction (CI) in the Chinese population.

Results

We recruited 164 CI patients and 167 healthy control subjects who were frequency-matched for age and gender. The frequencies of the -509TT genotype and T allele gene were significantly higher in the CI group (P = 0.007, P = 0.006). The frequencies of +869CC genotype and C allele were higher in the CI group (P = 0.002, P = 0.004). In the CI group, the individuals with -509TT genotype had a significantly higher level of plasma triglyceride (TG) (P = 0.017). +869CC genotype correlated significantly with higher level of plasma low density lipoprotein cholesterol (LDL-c) in the CI group (P = 0.015). With haplotype analysis, the frequency of the -509T/+869C combined genotype was significantly higher in the CI group than in controls (P < 0.001).

Conclusions

Our study suggests that C-509T and T869C gene polymorphisms in TGF-β1 may be a critical risk factor of genetic susceptibility to CI in the Chinese population.     

Regulation of blood pressure and glucose metabolism induced by L-tryptophan in stroke-prone spontaneously hypertensive rats

Background

Amino acids have been reported to act as modulators of various regulatory processes and to provide new therapeutic applications for either the prevention or treatment of metabolic disorders. The purpose of the present study is to investigate the effects of single oral dose administration and a continuous treatment of L-tryptophan (L-Trp) on the regulation of blood pressure and glucose metabolism in stroke-prone spontaneously hypertensive rats (SHRSP).

Methods

First, male 9-week-old SHRSP were administered 100 mg L-Trp·kg^-1 body weight in saline to the L-Trp group and 0.9% saline to the control group via a gastric tube as a single oral dose of L-Trp. Second, three groups of SHRSP were fed an AIN-93M-based diet supplemented with L-tryptophan (L-Trp) (0, 200, or 1000 mg·kg^-1 diet) for 3 weeks as continuous treatment of L-Trp.

Results

Single oral dose administration of L-Trp improved blood pressure, blood glucose, and insulin levels. Blood pressure, blood glucose, and insulin levels improved significantly in the L-Trp treatment groups. The administration of L-Trp also significantly increased plasma nitric oxide and serotonin levels.

Conclusion

L-Trp by both single oral dose administration and continuous treatment improves glucose metabolism and blood pressure in SHRSP.     

Effect of antioxidant capacity on blood lipid metabolism and lipoprotein lipase activity of rats fed a high-fat diet

OBJECTIVE: The present study explored the effect of antioxidant capacity on blood lipid metabolism and lipoprotein lipase (LPL) activity of rats fed with a high-fat diet (HFD). Furthermore, the relation of the atherosclerotic index (AI) and LPL activity to total antioxidant capacity (TAC) was studied. METHODS: Thirty-two Sprague-Dawley rats were randomly assigned to one of four groups (n = 8). The control group consumed an ordinary diet (5.1% fat, w/w). The other three experimental groups were fed with an HFD (14.1% fat, w/w), an HFD plus 0.1% lipoic acid (LA), or an HFD plus 0.1% N-acetylcysteine (NAC). After 4 wk, serum levels of triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol and LPL activity were examined. To evaluate rats' antioxidant status, TAC and superoxide dismutase activities and malondialdehyde level were measured. RESULTS: The HFD induced abnormal increases in lipid peroxidation, serum concentrations of total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol, and a decrease in high-density lipoprotein cholesterol concentration. Decreased activity of LPL, accompanied by a depressed antioxidant defense system, was observed in HFD-fed rats. These changes were partially restored in the NAC- and LA-treated groups. There was a negative correlation between AI and TAC (r = -0.969, P < 0.05). In addition, a significant positive correlation between LPL activity and TAC was found (r = 0.979, P < 0.05). CONCLUSION: Oxidative injury and lipid abnormalities were induced by an HFD. Administration of LA and NAC can improve the antioxidant capacity and activity of LPL and reduce blood lipid significantly. Antioxidant capacity is correlated with AI and LPL activity.     

beta-Carotene and canthaxanthin alter the pro-oxidation and antioxidation balance in rats fed a high-cholesterol and high-fat diet

This study investigated the effects of beta-carotene and canthaxanthin on lipid peroxidation and antioxidative enzyme activities in rats fed a high-cholesterol, high-fat diet. Wistar rats were divided into six groups. Negative control group (group NC) received a high-fat (150 g/kg) diet; cholesterol control group (group CC) received a high-cholesterol (10 g/kg), high-fat diet. The other four groups were fed a high-cholesterol, high-fat diet supplemented with crystal beta-carotene (group BC), beta-carotene beadlet (group BB), canthaxanthin beadlet (group CX) or alpha-tocopherol (group AT). Blood and livers were collected for analysis after 6 weeks of feeding. Group BB had significantly lower hepatic thiobarbituric acid reactive substance (TBARS) and conjugated diene concentrations, whereas group CX had a significantly lower plasma TBARS concentration than did group CC. In erythrocytes, glutathione peroxidase activities were significantly greater in groups BC, BB and CX than in group CC. Moreover, compared with group CC, catalase activities were significantly greater in groups BB and CX, and superoxide dismutase (SOD) activity was significantly greater in group BB. In livers, SOD activities were significantly greater in groups BC, BB and CX, and glutathione reductase activities were significantly greater in groups BB and CX than in group CC. Compared with group CC, hepatic retinol and alpha-tocopherol concentrations were significantly greater in groups BC, BB and CX, whereas plasma and hepatic cholesterol concentrations were significantly lower in group BC. These findings suggest that beta-carotene and canthaxanthin altered the pro-oxidation and antioxidation balance and suppressed cholesterol-induced oxidative stress via modulation of antioxidant system and cholesterol metabolism.     

Effects of supplemental cystine or methionine on growth and lifespan of stroke-prone spontaneously hypertensive rats

Stroke-prone spontaneously hypertensive (SHRSP) rats are considered a suitable model for studying the effects of dietary and other environmental factors on human essential hypertension and haemorrhagic stroke. To investigate the suitability of a control diet for this strain of rats, we studied the effects of supplementing casein and soya protein isolate (SPI) with two sulphur amino acids (methionine and cystine) on the growth and lifespan of SHRSP rats. The source of dietary protein and the type of supplemental sulphur amino acid had significant (P < 0.05) effects on food intake and weight gain measured after 31 d of the feeding study, while only the type of supplemental sulphur amino acid had significant effects on mean survival times and the survival rates. On average, the casein groups had higher food intake and weight gain compared with the SPI groups. The methionine-supplemented groups had lower food intake but higher weight gain than the cystine-supplemented groups. Similarly, the methionine-supplemented groups had higher mean survival times and survival rates compared with the cystine-supplemented groups. The data would suggest that a control diet based on cystine-supplemented casein (as recommended for normal healthy rats by the American Institute of Nutrition), may not meet the sulphur amino acid requirements for SHRSP rats, and that the methionine-supplemented casein would be an appropriate control diet for this animal model.     

Soymilk intake is associated with plasma and liver lipid profiles in rats fed a high-cholesterol diet

OBJECTIVE: This study investigated the effects of soymilk on lipid metabolism in Sprague-Dawley rats fed a cholesterol-enriched (0.3%) diet. METHODS: Thirty male Sprague-Dawley rats weighing 230.0 +/- 9.8 g were randomly assigned to one of three groups: control, S1 (containing 15% soymilk powder in the diet), and S2 (22.5%). After 8 wk, lipid profiles of the plasma, liver, and feces were determined. RESULTS: Body weight gain, daily food intake, and feeding efficiency showed no differences across groups (P > 0.05). The experimental groups had significantly lower plasma levels of cholesterol, triacylglycerol, and low-density lipoprotein cholesterol than the control group (P < 0.05) at weeks 4 and 8. However, total fecal excretion of neutral steroid did not significantly differ across groups (P > 0.05). CONCLUSION: Soymilk affects the metabolism of plasma cholesterol in Sprague-Dawley rats.     

Comparative effects of plant oils on the cerebral hemorrhage in stroke-prone spontaneously hypertensive rats

Objectives: Since oils and fats can induce metabolic syndrome, leading to cardiovascular and cerebrovascular diseases, the present study was performed to find out whether the plant oils affect the cerebral hemorrhage in stroke-prone spontaneously hypertensive (SHR-SP) rats.

Methods: From 47 days of age, male SHR-SP rats were given drinking water containing 1% NaCl to induce hypertension, and simultaneously fed semi-purified diets containing 10% perilla oil, canola oil, or shortening. The onset time of convulsion following cerebral hemorrhage was recorded, and the areas of hemorrhage and infarction were analyzed in the stroke brains.

Results: In comparison with 58-day survival of SHR-SP rats during feeding NaCl alone, perilla oil extended the survival time to 68.5 days, whereas canola oil shortened it to 45.7 days. Feeding perilla oil greatly reduced the total volume of cerebral hemorrhage from 17.27% in the control group to 4.53%, while shortening increased the lesions to 21.23%. In a microscopic analysis, perilla oil also markedly decreased the hemorrhagic and infarction lesions to 1/10 of those in control rats, in contrast to an exacerbating effect of shortening. In blood analyses, perilla oil reduced blood total cholesterol and low-density lipoproteins which were increased in SHR-SP, but canola oil further increased them and markedly lowered platelet counts.

Discussion: Perilla oil delayed and attenuated cerebral hemorrhage by improving hyperlipidemia in hypertensive stroke animals, in contrast to the aggravating potential of canola oil and shortening. It is suggested that perilla oil should be the first choice oil for improving metabolic syndrome in hypertensive persons at risk of hemorrhagic stroke.     

Dietary beta-carotene reduces serum lipid concentrations in spontaneously hypertensive rats fed a vitamin A-fortified and cholesterol-enriched diet.

The effects of dietary beta-carotene on serum lipid concentrations were examined in spontaneously hypertensive (SH) rats. Groups of SH rats were fed a semipurified, vitamin A-fortified and cholesterol-enriched diet supplemented with 0, 125, 250 or 500 mg beta-carotene/kg diet for a period of 44 d. beta-Carotene supplementation resulted in significant dose-related decreases in serum total, LDL and HDL cholesterol concentrations and serum total, VLDL and LDL triacylglycerol concentrations. The ratio of HDL cholesterol to total cholesterol was unchanged or slightly increased by dietary beta-carotene. The study suggests that dietary beta-carotene has antihyperlipidemic effects in SH rats. The effects in humans and the mechanism of the effects remain to be investigated.     

Supplementation with vitamin E and/or zinc does not attenuate atherosclerosis in apolipoprotein E-deficient mice fed a high-fat, high-cholesterol diet

Ever since oxidation has been known to be involved in atherogenesis, antioxidants have received considerable attention as potential antiatherogenic agents. The lipid-soluble vitamin E is the main antioxidant carried by lipoproteins. Zinc is a water-soluble trace element that acts as a cofactor of superoxide dismutase (SOD) and has an antioxidant role in several oxidative processes. To test the hypothesis that zinc could adjuvate the antioxidant activity of vitamin E and diminish atherogenesis, we explored how supplementing diet with vitamin E and/or zinc would affect an atherosclerosis-prone animal like Apo E-deficient mice. The increased plasma concentrations of both vitamin E and zinc showed that absorption was high. They had a significant hypolipidemic effect and the supplemented animals had 25% less plasma cholesterol and triglyceride than controls. The SOD activity was significantly higher in washed erythrocytes from mice supplemented with zinc. The plasma of supplemented animals was also significantly more resistant to oxidation. The size of lesions in the proximal aortic region did not differ among groups. Therefore, dietary supplementation resulted in the expected antioxidant effects but there was no substantial attenuation of atherosclerosis in this particular model.     

Alteration of serum lipoprotein metabolism by polychlorinated biphenyls and methionine in rats fed a soybean protein diet

The effects of dietary supplementation of methionine to a 20% soybean protein isolate diet on serum lipoprotein profiles and secretion rate of VLDL in rats receiving polychlorinated biphenyls (PCB) were investigated. Serum cholesterol levels were higher in rats fed PCB or a methionine supplement than in controls. The effects of PCB and methionine were synergistic. The feeding of PCB resulted in more cholesterol in all fractions of serum lipoproteins tested, especially HDL (HDL1 and HDL2). Dietary supplementation of methionine primarily increased HDL cholesterol. The elevation of serum lipoprotein cholesterol due to PCB and/or methionine was significant in HDL1, which showed alpha-mobility. These results showed that methionine and PCB significantly influenced HDL metabolism. The secretion rate of VLDL was higher in rats fed PCB than in controls, but the addition of methionine to diets did not affect the secretion rate of VLDL cholesterol. This implies that PCB increased serum cholesterol partly through the stimulation of VLDL cholesterol secretion.     

Effects of ascorbic acid on blood pressure and ascorbic acid metabolism in spontaneously hypertensive rats (SH rats)

Spontaneously hypertensive rats (SH rats) were administered drinking water containing 0, 200 or 1000 ppm ascorbic acid with or without 0.5% NaCl and the usual laboratory stock diet for 130 days. The rats given ascorbic acid with or without 0.5% NaCl had a lower mean systolic blood pressure level than that of the respective control group. The difference in the mean blood pressure level from that of the control group was 18-19 mmHg for 200 ppm ascorbic acid group and 30-40 mmHg for 1000 ppm ascorbic acid group. The SH rats were shown to have some defects of ascorbic acid metabolism by lower tissue ascorbic acid levels in the liver, lung and adrenals, and by lower response of ascorbic acid synthesis to a xenobiotic than the Wistar Kyoto rats, which served as the normotensive control rats for SH rats. The abnormalities of ascorbic acid metabolism in the SH rats may be associated with, in part, their high blood pressure, because exogenous ascorbic acid prevented the blood pressure elevation of SH rats, but some other mechanism may also be involved in the effect of ascorbic acid on blood pressure.