20两种实验性糖尿病模型小鼠的比较

目的：通过对链脲佐菌素（STZ）模型鼠和db／db模型鼠的糖尿病模型鼠的特点以及对三类降糖药反应性的比较,客观评价两种糖尿病模型鼠在药物研究中的应用价值。方法：离乳、雄性BALB／c小鼠高脂饲料喂养4周后,空腹12hSTZ（45mg／kg）腹腔注射,连续3次,一周后检测糖耐量受损、空腹血糖大于8．0mmol／L的为STZ模型鼠。将STZ模型鼠和8周龄空腹血糖大于8．0mmol／L的db／db模型鼠各随机分组,每组8只分别给予罗格列酮（12mg／kg）、格列苯脲（45mg／kg）、胰岛素（1U／kg）和生理盐水（0．1mL／10g）,每天1次,连续给药4周后检测两模型鼠及其对照组糖脂代谢相关的生化指标及激素水平。结果：STZ模型鼠和db／db模型鼠分别与正常BALB／c鼠、C57BL鼠对比,STZ模型鼠和db／db模型鼠均口服葡萄糖耐量试验（OG—TT）异常,空腹血糖、血TG和TC显著升高。但STZ模型鼠的胰岛素与C肽水平低于正常;而db／db鼠血C肽、胰岛素浓度显著升高;3种降糖药给药4周后STZ模型鼠的空腹血糖均明显降低,OGTT显著改善;罗格列酮对db／db模型鼠也可显著降低空腹血糖并改善糖耐量,但相同剂量的格列苯脲和胰岛素对db／db模型鼠的空腹血糖和糖耐量无影响。给予3倍剂量的胰岛素,db／db模型鼠才表现出空腹血糖的显著降低。结论：STZ模型鼠胰岛功能受损并有一定程度的胰岛素抵抗,对3种降糖药均敏感。db／db模型鼠表现出高度的胰岛素耐受,对内源性和外源性的胰岛素都不敏感,对罗格列酮的敏感性与STZ模型鼠相当。     

Effect of an antihypertensive drug, budralazine, on glucose and lipid metabolism in diabetic SHR

Budralazine was evaluated for its effects on glucose and lipid metabolism in diabetic SHR. SHR treated with 10% sucrose solution as drinking water for 3 months exhibited an impaired glucose tolerance with higher serum insulin levels and a reduction of sigma delta IRI/sigma delta BS. This model was, therefore, considered to resemble hypertensive patients with non-insulin-dependent diabetes (NIDD). Streptozotocin (30 mg/kg, i.v.)-treated SHR had a glucose intolerance with lower serum insulin levels and a reduction of sigma delta IRI/sigma delta BS, suggesting a similarity to hypertensive states with insulin-dependent diabetes (IDD) in humans. Repeated administration of budralazine (15-60 mg/kg/day, p.o.) had no effect on glucose tolerance, insulin secretion, serum electrolytes and lipid levels in Wistar rats, SHR, IDD-SHR and NIDD-SHR. Budralazine caused a significant decrease in systolic blood pressure in IDD-SHR and NIDD-SHR as well as in SHR. Repeated administration of furosemide (50-100 mg/kg/day, p.o.) resulted in a marked reduction in glucose tolerance, sigma delta IRI/sigma delta BS and serum potassium in Wistar rats. These effects of furosemide were more pronounced in SHR and IDD-SHR (IDD-SHR greater than SHR) and were reduced by either KC1 supplement or administration of triamterene. Thus, furosemide-induced glucose intolerance seems, at least partially, to be attributed to potassium loss which led to decreased insulin secretion. From these results, it is possible that budralazine may be useful for the treatment of hypertensive patients with diabetes.     

EFFECTS OF DC-015, A NOVEL POTENT AND SELECTIVE α1-ADRENOCEPTOR ANTAGONIST ON PLASMA LIPID AND VASCULAR REACTIVITY IN HYPERLIPIDAEMIC RATS

1. The effects of DC-015, a newly synthesized quinazoline derivative, on plasma lipids, lipoprotein levels and vascular reactivity were investigated in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). 2. The hypotensive effect of DC-015 was compared with prazosin in SHR. Intravenous administration of DC-015 and prazosin (both at 0.01, 0.05 and 0.1mg/kg) induced dose-dependent reductions in mean arterial pressure (MAP) which reached a maximal effect 5 min after injection and persisted over 2 h in SHR. DC-015 decreased MAP with equal efficiency compared with prazosin. 3. The plasma levels of total cholesterol (CE), low-density lipoprotein (LDL)-CE and total triglyceride (TG) were markedly increased and the levels of high-density lipoprotein (HDL)-CE were markedly decreased in both high fat-high cholesterol (HF-HC) diet fed WKY and SHR. 4. In HF-HC diet fed WKY and SHR, the total plasma CE, LDL-CE and total plasma TG were significantly reduced after oral administration of DC-015 (1 mg/kg, twice a day) for 4 weeks. Furthermore, DC-015 therapy was associated with increased HDL-CE levels and thus the ratio of total CE to HDL-CE was improved. The antihyperlipidaemic effect of prazosin was less than that of DC-015. 5. Significantly attenuated median effective concentration (EC₅₀) values and augmented maximal responses for phenyl-ephrine-induced contraction of aortic rings were observed in HF-HC diet fed WKY and SHR. Endothelium-dependent relaxation to acetylcholine was impaired while endothelium-independent relaxation to nitroglycerin was well preserved. 6. Oral administration of DC-015 (1 mg/kg, twice a day) for 4 weeks significantly augmented EC₅₀ values and attenuated maximal responses for phenylephrine-induced contraction of aortic rings in HF-HC diet fed WKY and SHR. Prazosin (1 mg/kg, twice a day) showed a lesser extent of efficiency than DC-015 at normalization of vasorelaxation in HF-HC diet fed WKY and SHR. 7. It is concluded that DC-015, a potent antihypertensive agent, may have additional advantage in also reducing hyperlipidaemia.     

二苯乙烯类化合物E1的降糖作用及其机制的初步研究

目的　观察灌胃给予二苯乙烯类化合物E1对实验性非胰岛素依赖性糖尿病 (NIDDM )大鼠的降糖作用。方法　通过尾静脉注射小剂量链佐菌素 (streptozotocin ,STZ)来损伤大鼠胰岛细胞造成其糖耐量异常 ,继而喂以高糖 -高脂饲料来诱发动物肥胖形成的Ⅱ型糖尿病大鼠模型。结果　灌胃给予二苯乙烯类化合物E1能明显降低NIDDM大鼠空腹血糖、葡萄糖耐量实验 (OGTT)各时间点的血糖值 ;二苯乙烯类化合物E1.0 1mmol·L-1及 0 0 0 1mmol·L-1对βTC3 细胞无刺激其分泌胰岛素作用。结论　二苯乙烯类化合物E1的降糖作用并非通过刺激胰岛素的分泌 ,而可能是通过增加胰岛素作用效率     

Effects of Ginkgo biloba extract on blood pressure and vascular endothelial response by acetylcholine in spontaneously hypertensive rats

We previously demonstrated that Ginkgo biloba extract (Ginkgo) produced vasodilation via the nitric oxide pathway in aortic segments isolated from Wistar rats. In this study, we have analysed the effects of daily long-term oral Ginkgo treatment on blood pressure, vascular tone, and calcium mobilization to evaluate the clinical availability. Spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were fed either a control diet or a diet containing 0.05%-0.5% Ginkgo for 30 days. Administration of Ginkgo did not change systolic blood pressure in WKY, but significantly decreased systolic blood pressure in SHR. In thoracic aortic preparations isolated from SHR, diminished relaxation in response to acetylcholine was improved by a Ginkgo-containing diet. This diet significantly decreased the EC50 value and significantly increased maximum relaxation in response to acetylcholine in SHR. In aortic segments isolated from WKY, acetylcholine-induced relaxation was not affected by a Ginkgo-containing diet. Sodium nitroprusside-induced relaxation was unchanged by a Ginkgo-containing diet in SHR and WKY. We also examined the effects of a Ginkgo-containing diet on the intracellular calcium level of aortic endothelium using a fluorescent confocal microscopic imaging system. Calcium Green 1/AM preloading indicated that acetylcholine significantly increased the endothelial intracellular calcium level. The Ginkgo-containing diet significantly enhanced this increase in the aortic endothelium of SHR, but did not change that of WKY. The results suggested that Ginkgo enhanced endothelium-dependent vasodilation and elevation of the endothelial intracellular Ca(2+) level in SHR, resulting in hypotension. This accelerative effect of Ginkgo on Ca(2+) mobilization seemed to be associated with restoration of impaired dilatory function induced by acetylcholine in endothelial cells.     

高脂高盐饮食对未成年鼠生长及代谢的影响

目的 观察高脂高盐饮食对未成年鼠生长发育、胰岛素敏感性及相关代谢指标的影响. 方法 40只体质量50g左右SD鼠（生长至3周末,刚断乳）随机分为三组：普通饮食组（NC组）12只、高脂组（FC组）14只、高脂高盐组（FSC组）14只,分别给予普通食物、高脂食物、高脂＋高盐食物喂养4周（鼠生长至7周末）,观察三组大鼠体质量、血压及内脏脂肪重量、血脂等,行口服葡萄糖耐量试验及胰岛素释放试验评价血糖及胰岛细胞功能. 结果 FSC组鼠体质量、内脏脂肪、血糖及胰岛素水平均较NC组明显增加,血脂紊乱加重并表现出显著的胰岛素抵抗,差异有统计学意义（均P＜0.05）. 结论 高脂高盐饮食可诱导未成年鼠腹型肥胖、高血压、血脂异常及糖耐量异常.     

甲壳低聚糖对饲高糖高脂大鼠血糖的调节作用

目的观察甲壳低聚糖(COS)对注射小剂量链脲佐菌素(STZ)及饲高糖高脂大鼠血糖的影响。方法大鼠随机分为2组:正常对照组10只,喂基础饲料;造模组40只,经腹腔注射小剂量STZ后,用基础饲料喂养2周,挑选葡萄糖耐量异常者20只又随机分为2组:高糖高脂对照组10只和COS干预组10只,两组均用高糖高脂饲料喂养,同时COS干预组用COS溶液灌胃给药。各组连续观察16周,定期测定体重、空腹血糖及胰岛素水平,实验结束前通过葡萄糖耐量试验来观察胰岛β-细胞功能变化。结果 COS干预组与高糖高脂组比较,体重、空腹血糖和胰岛素水平差异显著(P<0.05或0.01),葡萄糖耐量异常得到明显改善(P<0.05)。结论 COS有降低高糖高脂饲料大鼠血糖水平,增强糖耐量的作用。     

2型糖尿病大鼠模型的建立与评价

目的：建立具有胰岛素抵抗特征、发病过程近似于人类2型糖尿病的动物模型。方法：雄性Wistar大鼠喂以富含不饱和脂肪酸的特殊高脂肪膳食5周，诱发出胰岛素抵抗．继之以小剂量链脲佐菌素（STZ，25mg／kg，腹腔注射）导致胰岛素代偿性分泌障碍，诱发高血糖症。应用正常血糖-高血浆胰岛素钳夹技术评价大鼠的胰岛素敏感性。结果：与常规饲料喂养大鼠相比，高脂膳食组的葡萄糖输注率显著降低，空腹血浆胰岛素显著升高。STZ注射后1周高脂膳食组大鼠血糖中度升高，血胰岛素下降，但仍高于普通饲料喂养组，且高脂血症和胰岛素抵抗继续存在。高脂饲料喂养组及高脂饲料＋小剂量STZ注射组大鼠的葡萄糖输注率显著低于正常对照组。结论：通过高脂膳食结合小剂量STZ注射成功复制出了实验性2型糖尿病动物模型，它是研究2型糖尿病发病机制、药物研究和胰岛素抵抗相关疾病的理想动物模型．     

Effects of red mold dioscorea with pioglitazone,a potentially functional food,in the treatment of diabetes

The prevalence of type 2 diabetes mellitus is increasing rapidly, and its treatment with pioglitazone is likely to induce rhabdomyolysis. We aimed to determine the effect of cotreatment with pioglitazone and red mold dioscorea (RMD) produced by Monascus purpureus NTU 568 on pancreas function in streptozotocin (STZ)-induced diabetic rats. In diabetic rats fed RMD, RMD with pioglitazone, and pioglitazone alone, insulin concentrations increased significantly by 18.6–40.4%, 64.0–100.0%, and 52.8%, respectively, compared with that in the diabetic group (p < 0.05). Oral glucose tolerance was impaired in the STZ-induced diabetic group within 4 weeks, however, oral glucose tolerance in rats treated with RMD or RMD with pioglitazone improved after 4 weeks, 6 weeks, and 8 weeks. Findings from this study might lend support to the use of RMD as a novel functional food for the prevention of diabetes.     

Long-term feeding of red algae (Gelidium amansii) ameliorates glucose and lipid metabolism in a high fructose diet-impaired glucose tolerance rat model

This study was designed to investigate the effect of Gelidium amansii (GA) on carbohydrate and lipid metabolism in rats with high fructose (HF) diet (57.1% w/w). Five-week-old male Sprague-Dawley rats were fed a HF diet to induce glucose intolerance and hyperlipidemia. The experiment was divided into three groups: (1) control diet group (Con); (2) HF diet group (HF); and (3) HF with GA diet group (HF + 5% GA). The rats were fed the experimental diets and drinking water ad libitum for 23 weeks. The results showed that GA significantly decreased retroperitoneal fat mass weight of HF diet-fed rats. Supplementation of GA caused a decrease in plasma glucose, insulin, tumor necrosis factor-α, and leptin. HF diet increased hepatic lipid content. However, intake of GA reduced the accumulation of hepatic lipids including total cholesterol (TC) and triglyceride contents. GA elevated the excretion of fecal lipids and bile acid in HF diet-fed rats. Furthermore, GA significantly decreased plasma TC, triglyceride, low density lipoprotein plus very low density lipoprotein cholesterol, and TC/high density lipoprotein cholesterol ratio in HF diet-fed rats. HF diet induced an in plasma glucose and an impaired glucose tolerance, but GA supplementation decreased homeostasis model assessment equation-insulin resistance and improved impairment of glucose tolerance. Taken together, these results indicate that supplementation of GA can improve the impairment of glucose and lipid metabolism in an HF diet-fed rat model.     

A comparative study on hypoglycemic and hypocholesterolemic effects of high and low molecular weight chitosan in streptozotocin-induced diabetic rats.

The hypoglycemic and hypocholesterolemic effects of high and low molecular weight chitosan were evaluated in streptozotocin (STZ)-induced diabetic rats. Rats were divided into three groups of normal rats (Experiment I) and three groups of diabetic rats (Experiment II). The first group received a cellulose (control) diet, the second group received a low MW (1.4 x 10(4)Da) chitosan diet and the third group received a high MW (1.0 x 10(6)Da) chitosan diet. All three diets were containing 0.5% cholesterol. Experiment I: rats fed with high MW or low MW chitosan diet had increased high density lipoprotein (HDL) cholesterol. However, chitosan did not affect plasma glucose in normal rats. Experiment II: significantly decreased plasma glucose and total cholesterol and increased HDL cholesterol and fecal cholesterol excretion were observed in diabetic rats fed with high MW chitosan diet than animals fed with cellulose diet. However, no statistical significant difference in plasma glucose and total cholesterol was observed in diabetic rats fed with low MW chitosan. The total content of SCFAs in cecum was significantly increased and the ratio of acetate to propionate was slight but significantly decreased in diabetic rats after consuming high MW chitosan diet. The activities of hepatic hexokinase were significantly increased and the intestinal disaccharidases including sucrase and maltase were significantly decreased in normal and diabetic rats fed with high MW chitosan diet. Results obtained from the present study demonstrated the potential of high MW chitosan in reducing hyperglycemia and hypercholesterolemia in STZ-induced diabetic rats.     

Gender differences in blood pressure and heart rate in spontaneously hypertensive and Wistar-Kyoto rats

1. In general, premenopausal women are known to have lower blood pressure than men and animal models have shown a similar sexual dimorphism. However, many studies in animals have been performed using anaesthetized or restrained models. Current experiments were conducted to investigate the relationships among resting heart rate, blood pressure and gender in conscious, unrestrained normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. Biotelemetry transmitters were implanted in 6-month-old animals. Values for heart rate, diastolic blood pressure, systolic blood pressure and pulse pressure were recorded continuously at 10 min intervals after all animals recovered completely from surgery. 3. Normal circadian rhythms in heart rate were found in all rats, with no significant differences among the four groups; the circadian variation in blood pressure was evident in all groups, although much smaller. Heart rate was found to be higher in WKY female rats than in the other three groups. Male WKY rats, male SHR and female SHR had similar heart rates. Male SHR had significantly higher systolic and diastolic blood pressures than female SHR. Male and female WKY rats had similar diastolic blood pressure, but males had slightly higher systolic pressure than females. No significant difference in pulse pressure was found in WKY male and female rats. Male SHR showed significantly higher pulse pressure than female SHR at most times during the day. 4. In conclusion, these results indicate that hypertension is exacerbated in male SHR compared with females under conscious resting conditions and demonstrate that the higher heart rate observed in WKY female rats is not present in the SHR model.     

丹皮多糖-2b对2型糖尿病大鼠的抗糖尿病作用

目的 研究丹皮多糖-2b(CMP-2b)对2型糖尿病(T2DM)大鼠的抗糖尿病作用。方法 给大鼠iv小剂量链脲霉素(streptozocin,STZ)加高热量饲料喂养复制T2DM大鼠模型,连续po 4～5周,测定各实验动物体重、食和水摄取量、空腹血糖、葡萄糖耐量、血脂、胰岛素及胰岛素受体(InsR)。结果 CMP-2b能显著降低T2DM大鼠食和水摄取量,FBG,总胆固醇及甘油三脂水平;改善葡萄糖耐量;提高肝细胞膜低亲和力InsR最大结合容量(B_max2)及胰岛素敏感性指数(ISI)。结论 CMP-2b可能对T2DM及其并发症有一定的治疗作用。     

小牛血清去蛋白注射液对2型糖尿病合并脑梗死模型大鼠胰岛素抵抗的影响

目的:观察小牛血清去蛋白注射液(DCBI)对2型糖尿病合并脑梗死模型大鼠血糖、血脂代谢的影响及其对胰岛素抵抗(IR)的改善作用。方法:大鼠用高脂高糖饮食伴尾静脉注射链脲佐菌素复制2型糖尿病模型,成功后再建立大鼠大脑中动脉栓塞模型,分为模型组、假手术组、DCBI(低、高剂量,30、60mg·kg-1·d-1,腹腔注射)组和对照药罗格列酮组;并设立正常组。各组给予相应试药5周后,测定空腹血糖(FBG)、血清胰岛素(FI NS)、糖耐量(OGTT)水平,并计算胰岛素抵抗指数(IRI)、胰岛素敏感指数(ISI),测定总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、游离脂肪酸(NEFA)水平。结果:与模型组比较,DCBI治疗后可显著降低2型糖尿病合并脑梗死模型大鼠FBG水平及增强糖耐量(P<0.01),对FI NS水平的改变不明显(P>0.05);改善机体对胰岛素的抵抗性(P<0.01或P<0.05);并明显降低TC、TG、LDL-C、NEFA水平及升高HDL-C水平(P<0.01),改善高脂状态。结论:DCBI可降低2型糖尿病合并脑梗死模型大鼠血糖,调节血脂代谢紊乱,具有改善IR的作用。     

BLOOD PRESSURE, SALT APPETITE AND MORTALITY OF GENETICALLY HYPERTENSIVE AND NORMOTENSIVE RATS MAINTAINED ON HIGH AND LOW SALT DIETS FROM WEANING

1. Blood pressure, bodyweight, saline preference and mortality rate were examined in spontaneously hypertensive rats (SHR) of the Okamoto strain and normotensive control Wistar-Kyoto (WKY) rats maintained on low (0.1% NaCl w/w), control (0.8% w/w) and high (3% w/w) salt diets from weaning until 6 months of age. 2. The growth rate of SHR on high salt diet was not significantly different from that on control diet but SHR maintained on a low salt diet exhibited a markedly reduced growth rate. While the growth rate of WKY on low salt diet was not significantly different from that on control diet, the bodyweights of WKY on high salt diet were significantly greater than those of animals on control diet. 3. While low salt diet markedly attenuated the development of hypertension in the SHR, high salt diet significantly exacerbated the blood pressure of this strain. Neither high nor low salt diet altered the blood pressure of WKY. 4. SHR on high and low salt diets had an increased mortality rate compared with SHR on control salt diet but these differences were of slight statistical significance. Conversely, WKY on all three diets exhibited similar mortalities over the 6-month observation period. There were no significant differences in mortalities between SHR and WKY on any diet. 5. The preference for 0.9% saline, when offered as a choice with water, was not significantly different between SHR on the different diets. WKY on high salt diet, however, exhibited a significantly reduced preference for saline over the 10-day test period compared with animals on control or low salt diet. 6. Thus dietary salt modulates the hypertension of SHR but not the blood pressure of WKY. SHR would appear to require more dietary sodium for normal growth and perhaps full expression of its hypertension. The higher and lower blood pressures of the SHR on high and low salt diet, respectively, were associated with increased mortality, which was a trend not seen in the WKY.     

Pioglitazone can ameliorate insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats

Aim: To investigate the effect of the peroxisome proliferator-activator receptor (PPAR)-γ agonist, pioglitazone, on insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats. Methods: Normal female Wistar rats were injected intraperitoneally with low-dose streptozotocin (STZ, 30mg/kg) and fed with a high sucrose-fat diet for 8 weeks. Pioglitazone (20mg/kg) was administered orally to the obese and insulin-resistant rats for 28d. Intraperitoneal glucose tolerance tests, insulin tolerance tests and gluconeogenesis tests were car ried out over the last 14d. At the end of d 28 of the treatment, serums were collected for biochemical analysis. Glucose transporter 4 (GLUT4) and insulin receptor substrate-1 (IRS-1) protein expression in the liver and skeletal muscle were detected using Western blotting. Results: Significant insulin resistance and obesity were observed in low-dose STZ and high sucrose-fat diet induced obese rats. Pioglitazone (20mg/kg) treatment significantly decreased serum insulin,triglyceride and free fatty acid levels, and elevated high density lipoprotein-cholesterol (HDL-C) levels. Pioglitazone also lowered the lipid contents in the liver and muscles of rats undergoing treatment. Gluconeogenesis was inhibited and insulin sensitivity was improved markedly. The IRS-1 protein contents in the liver and skeletal muscles and the GLUT4 contents in skeletal muscle were elevated significantly. Conclusion: The data suggest that treatment with pioglitazone improves insulin sensitivity in low-dose STZ and high sucrose-fat diet induced obese rats. The insulin sensitizing effect may be associated with ameliorating lipid metabolism, reducing hyperinsulinemia, inhibiting gluconeogenesis, and increasing IRS-1 and GLUT4 protein expression in insulin-sensitive tissues.     

益气养阴清热液对高血糖肥胖大鼠胰岛素抵抗的影响

目的观察益气养阴清热液(YYQ)对高血糖肥胖大鼠胰岛素抵抗的改善作用。方法采用高脂饲料加小剂量链脲佐菌素(STZ)诱导高血糖肥胖大鼠胰岛素抵抗,用YYQ治疗4wk。检测空腹血糖(FBG)、葡萄糖耐量(OGT)、血清胰岛素(INS)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、游离脂肪酸(FFA)、红细胞膜胰岛素受体(INSR)、胰岛素钳夹实验下的葡萄糖输注率(GIR);测定肾周、附睾周围脂肪垫重量。同时测定YYQ对肝组织中IR-1、IRS-1mRNA表达的影响。结果YYQ治疗4wk后,大鼠血清中TC、TG、LDL-C、INS、FFA降低,OGT改善,而血清中HDL-C和GIR明显升高,INSR高、低亲和力受体数目均明显增多,肝组织中IR、IRS-1mRNA表达升高,各项指标均与模型组大鼠差异有显著性。结论YYQ对高血糖肥胖大鼠胰岛素抵抗有治疗作用,通过增加胰岛素受体数目而提高其胰岛素敏感性可能是其作用机制之一。     

Differential amino acid transmission in the locus coeruleus of Wistar Kyoto and spontaneously hypertensive rats

In addition to differences in their blood pressure, Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) are known to differ in their emotional behaviour. The neurochemistry underlying these differences is not well understood. In the present study the release rates of the two main regulatory amino acids in the locus coeruleus, glutamate and gamma-aminobutyric acid (GABA), were monitored in WKY rats and SHR to investigate whether basal and/or challenged neurotransmission differs between these strains. The strains differed in their basal blood pressure (WKY 102±2 mmHg, SHR 140±4 mmHg), as well as in their emotional behaviour, since WKY rats displayed enhanced anxiety-related behaviour in the open field test (time in centre: WKY 197±40 s/30 min, SHR 741±93 s/30 min). Basal glutamate and GABA release rates did not differ between WKY rats and SHR. A rise in blood pressure induced by intravenous infusion of noradrenaline for 10 min enhanced GABA release in WKY rats by 60%, while no effect was observed in SHR. Glutamate release did not respond to experimental hypertension in both strains. Intravenous infusion of sodium nitroprusside led to a fall in blood pressure, which was less pronounced and was of shorter duration in WKY rats than in SHR. The depressor response had no effect on amino acid release in the locus coeruleus of both strains. Mild stress induced by noise or tail pinch led to slight rises in arterial blood pressure (10 mmHg and 20 mmHg respectively), which were similar in WKY rats and SHR. Tail pinch enhanced the release rates of glutamate and GABA in the locus coeruleus of WKY rats and SHR; however, no strain differences were noted. Noise stress did not significantly influence amino acid release. These findings demonstrate that SHR and WKY rats differ in GABAergic neurotransmission, which is revealed in response to specific cardiovascular challenges, but not to mild stressors. The observed lack of GABA response to blood pressure elevation in SHR may reflect a disturbed mechanism counteracting high blood pressure, possibly contributing to hypertension in this strain.     

EFFECT OF SALT LOADING ON BLOOD PRESSURE AND EICOSANOID METABOLISM OF SPONTANEOUSLY HYPERTENSIVE RATS FED A FISH OIL ENRICHED DIET

This study investigated the effects of dietary modification of prostaglandin (PG) synthesis on blood pressure regulation in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats under conditions of normal and elevated salt intake. After an initial period of 4 weeks on either a 2-series PG 'inhibitory' diet of fish oil (maxEPA) or a control diet of saturated fat, half of each group received 1.5% saline for 1 week. Blood pressures were unaffected by diet during the period of normal salt intake, but following salt loading, the maxEPA-fed SHR showed a blood pressure increase (mean = 21 mmHg) relative to the EPA-fed rats on water. Rats on maxEPA showed impaired ability to generate serum thromboxane and diminished excretion of urinary 6-keto-PGF1 alpha and PGE2. SHR on water showed greater serum TXB2 generating capacity than WKY, but diminished urinary PGE2 excretion. Thus, the increased blood pressure observed in the salt-loaded SHR on the maxEPA diet may be explained by reduced renal PG synthesis resulting in either mild sodium retention and/or increased vascular reactivity.     

Effect of chronic treatment of propranolol on lipid metabolism in spontaneously hypertensive rats (SHR)

The effects of propranolol on lipid metabolism were studied in spontaneously hypertensive rats (SHR). Male SHR and corresponding Wistar Kyoto rats (WKY) were used at 5 weeks of age. The SHR were given 10 mg/kg/day of dl-propranolol . HCl by gavage for 10 weeks. Body weight gain in untreated SHR and propranolol-treated SHR (SHR-P) groups were low, as compared with those of the WKY group. Total cholesterol, phospholipid and total lipid of the serum and liver in the SHR-P group were higher than in the SHR group. In the early weeks of treatment, serum triglyceride and non-esterified fatty acid levels in the SHR-P group were slightly lower than those in the SHR group. Aortic lipid levels in the SHR-P group were lower than those in the SHR group. During the later weeks of treatment, blood glucose level in the SHR-P group was higher than in the SHR group. The serum immunoreactive insulin value in the SHR-P group was slightly lower than in the SHR group. These results may suggest that propranolol inhibits hormone-sensitive lipase activity in the early weeks of treatment and influences cholesterol biosynthesis and/or catabolism.