Alteration of the intracellular calcium pool of adipose tissue in spontaneously hypertensive rats

The intracellular calcium pool of adipose tissue was estimated by studying the kinetics of⁴⁵Ca efflux from the tissue of 9-week old spontaneously hypertensive (SHR) and normotensive Kyoto-Wistar (NKWR) rats subjected to peripheral immunosympathectomy (nerve growth factor antiserum treatment of newborn rats) and in intact (shamtreated) animals of both strains. The development of hypertension in SHR was prevented by immunosympathectomy, however, both groups, SHR-intact and immunosympathectomized rats showed an increase in the intracellular calcium content of adipocytes. These results indicate that the alteration of the membrane control over intracellular calcium distribution in adipose tissue of SHR cannot be attributed to an enhanced activity of the sympathetic nervous system.     

Adipose tissue lipoprotein lipase (LPL) and triglyceride uptake in Zucker rats

To investigate the relationship between elevated adipose tissue lipoprotein lipase (LPL) activity and triglyceride uptake in Zucker obese rats, fed and 12 hour fasted female obese and lean Zucker rats were given intrajugular infusion of radio-labelled triglyceride and label clearance and uptake were examined over 35 minutes. In the fed state, obese rats showed more rapid clearance of the label from the bloodstream and, in both fed and fasted states, greater uptake into retroperitoneal and parametrical fat pads than lean rats. Obese rats showed proportionally less uptake into heart and liver. Regardless of feeding condition, obese rats exhibited elevations in adipose tissue LPL, which was significantly correlated with label uptake in adipose tissue. These results show that, in Zucker obese rats, elevated adipose tissue LPL is associated with increased adipose tissue triglyceride uptake. A preferential “shunting of calories” into adipose tissue, which is presumably mediated by LPL, could underlie the intractability of the Zucker obesity syndrome as well as the altered feeding behavior of Zucker obese rats.     

Increased sensitivity of adipose tissue of spontaneously hypertensive rats to ACTH

The action of ACTH on lipolysis was studied in the adipose tissue of rats with spontaneous and renal hypertension and also in normotensive rats of corresponding control groups. The sensitivity of the adipose tissue of SHR rats to ACTH was shown to be higher than in the normotensive control. Evidence was obtained that this increase in sensitivity is due to the state or quantity of intracellular calcium. In rats with renal hypertension no such increase in sensitivity of their adipose tissue to ACTH was found.Department of Pathomorphology, No. 4, Board, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR E. I. Chazov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp. 23–26, July, 1979.     

Acquisition of conditioned suppression and responsivity to thermal stimulation in spontaneously hypertensive,renal hypertensive and normotensive rats

The acquisition of conditioned suppression of instrumental responding and responsivity to thermal stimulation were assessed in spontaneously hypertensive rats of the Okamoto-Aoki strain (SHRs), renal hypertensive rats of the Wistar-Kyoto strain (WKYs), and normotensive WKY rats. Spontaneously hypertensive rats showed significantly faster acquisition of conditioned suppression than age-matched WKY normotensive rats. This acquisition difference between SHRs and normotensive WKYs was maintained even following chronic preexposure to shock alone; a treatment that retarded normal acquisition of conditioned suppression. In contrast, renal hypertensive WKYs acquired conditioned suppression at the same rate as age-matched normotensive WKYs. Spontaneously hypertensive rats and renal hypertensive WKYs both showed significantly longer latencies than normotensive WKYs to respond to thermal stimulation using a hot-plate assay. These outcomes suggest that the relationship between blood pressure and the acquisition of conditioned suppression in SHRs is either pleiotrophic or a consequence of random fixation, and that acquisition of conditioned suppression may serve as a valuable marker variable of hypertension in the SHR. The dissociation between acquisition of conditioned suppression and responsivity to thermal stimulation suggests that different mechanisms may mediate nociceptive responses to shock and thermal stimulation in these models of hypertension.     

高血压大鼠血管外周脂肪组织对血管调节功能的改变及他汀类药物治疗的影响

目的：观察自发性高血压大鼠 (SHR) 血管外周脂肪组织释放血管舒张因子功能的改变及他汀类药物干预的影响。方法:SHR 10周龄后，分别给予阿托伐他汀钙50 mg/kg·d,血脂康 2 400 mg/kg·d干预16周。观察阿托伐他汀钙干预组（SHR-A）、血脂康干预组（SHR-X）、对照SHR组和WKY组的血压（SBP）变化；于26周龄，把各组大鼠的相邻的两段胸主动脉环分为血管外周脂肪亚组和裸血管亚组，予10-6 mmol/L苯肾上腺素(PHE)刺激,比较两亚组血管收缩力的差异;用液体转移的方法,观察孵育血管外周脂肪组织的培养液对裸血管张力的影响。结果:① WKY组、SHR-A组、SHR-X组SBP实验前后无显著变化，SHR组的SBP实验结束时显著高于实验开始时；② WKY组、SHR-A组、SHR-X组血管外脂肪亚组的收缩力低于裸血管亚组的收缩力,而SHR两血管亚组的收缩力无差别;③ 把WKY组，SHR-A组，SHR-X组孵育的血管外脂肪的培养液转移到裸血管均诱发其快速舒张，而SHR组则无显著血管舒张反应。结论：WKY的血管外周脂肪组织释放一种可转移性血管舒张因子，降低血管对苯肾上腺素的反应性,调节血管功能而SHR的血管外周脂肪组织这种血管调节作用减弱;血管外周脂肪组织这种功能异常可能是高血压血管功能异常的病理基础之一他汀类药物治疗在修复SHR血管外周脂肪组织这种功能异常的同时,还能减缓SHR血压上升。     

Biosynthesis of renal prostaglandins in spontaneously hypertensive rats

The biosynthesis of prostaglandins (PG) E₂ and F₂ from [¹⁴C]arachidonic acid by renal medullary tissue of rats with spontaneous hypertension and of normotensive Wistar rats was investigated at different ages (1.5 and 3.5 months). In animals with spontaneous hypertension the synthesis of PG E₂ from arachidonic acid was at a much lower level than in Wistar rats. The biosynthesis of PG F₂ in these animals was virtually indistinguishable from normal. No age differences were found in PG formation by the kidneys of rats with spontaneous hypertension, whereas in Wistar rats PG E₂ biosynthesis was depressed at the age of 3.5 months.Laboratory of Pathophysiology, Institute of Pediatrics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 6, pp. 659–661, June, 1977     

Evidence of altered calcium accumulation and calcium binding by the membranes of adipocytes in spontaneously hypertensive rats

Calcium accumulation and calcium binding (ATP-dependent and ATP-independent calcium uptake) by the fragmented plasma membrane, the cytoplasmic reticulum and the mitochondria of isolated adipocytes obtained from spontaneously hypertensive (SHR, Kyoto-Wistar) and normotensive Wistar and Kyoto-Wistar rats were studied by means of isotopic (⁴⁵Ca) exchange in vitro.The value of Ca accumulation in the cytoplasmic reticulum fraction of adipocytes obtained from SHR was found decreased, while in the mitochondrial fraction it was considerably greater as compared to those in both normotensive control groups. Ca binding (ATP-independent) by the plasma membrane fraction of hypertensive rats was less than that of the normotensive rats. There was no difference between the groups studied in calcium binding ability for the cytoplasmic reticulum fraction of adipocytes.These results seem to indicate that the adipose cells of hypertensive rats have an alteration of the membrane mechanism maintaining intracellular calcium distribution.     

Decrease of calcium binding by the red blood cell membrane in spontaneously hypertensive rats and in essential hypertension

Ca binding in the red blood cell (RBC) membrane of spontaneously hypertensive rats (SHR) and of patients with essential hypertension was studied. Under conditions of physiological concentration of free Ca in the incubation medium of RBC the outer part of the membrane binds 393±32 and 435±30 nmole of Ca per ml of RBC in rats and humans, respectively, without essential differences in the amount of Ca in hypertensive individuals as compared to the normotensive controls.The membrane of red blood cell ghosts (RBCgh) at concentrations of free Ca corresponding to its intracellular concentration binds 4.28±0.39 and 3.53±0.15 nmole of Ca per mg of protein of RBCgh in rats and humans, respectively. This part of membrane-bound Ca pool (most probably related to the inner part of the red blood cell membrane) is reduced by 48% in SHR and by 28% in patients with essential hypertension as compared to normotensive controls.It is suggested that the decrease of Ca binding ability of the RBC membrane in both types of hypertension studied may be a pattern of a more widespread cell membrane defect.     

Altered permeability of the erythrocyte membrane for sodium and potassium ions in spontaneously hypertensive rats

Summary Permeability of the erythrocyte membrane for sodium and potassium ions was studied in 8–10-week old spontaneously hypertensive rats (SHR, Kyoto Wistar strain), normotensive Wistar and Sprague-Dawley rats.The rate constant of Na/Na exchange was considerably greater in the SHR than in the normotensive Wistar and Sprague-Dawley rats. This difference remained the same in the rats adrenalectomized 7 days prior to the experiment. The maximum difference in the constants was found when the sodium pump was blocked by ouabain.The accumulation of⁴²K in the erythrocytes of the SHR (the sodium pump being blocked) took place at a considerably slower rate, and the K⁺ washout into a potassium-free medium was faster than in the normotensive Wistar and Sprague-Dawley rats.These results seem to indicate a higher permeability of the SHR's erythrocyte membrane for Na⁺ and K⁺ions, as compared to normotensive Wistar and Sprague-Dawley strains. It is suggested that the increased permeability of the erythrocyte membrane for Na⁺ and K⁺ in the SHR may reflect a more widespread cell membrane defect, which could serve as a general cause for activating the mechanisms maintaining high blood pressure.     

Alteration of intracellular calcium distribution in the adipose tissue of human patients with essential hypertension

The in vitro study of the kinetics of⁴⁵Ca efflux from human adipose tissue (omentum major) reveals three pools of exchangeable calcium. The most rapidly exchangeable pool (A) corresponds to extracellular calcium, the two more slowly exchangeable pools (B and C), to intracellular calcium.In the adipose tissue of patients with essential hypertension, the calcium content of the two intracellular pools is increased by 71% and 83%, respectively, as compared to that in normotensive patients.     

Some changes in adrenalin lipolysis in adipose tissue in rats with spontaneous and renal hypertension

Lipolysis was studied in adipose tissue of adrenalectomized and intact rats with hypertension (spontaneous or renal) and in normotensive rats of the corresponding control groups. The degree of lipolysis (in the presence or absence of adrenalin) was judged from the quantity of nonesterified fatty acids in the tissue and the liberation of glycerol into the incubation medium in vitro. The response of adipose tissue to the action of adrenalin in the hypertensive and control animals was the same provided the adrenals were intact. Preliminary adrenalectomy, abolishing the effect of corticosteroid secretion, reduced the lipolytic response of the adipose tissue to adrenalin in control normotensive rats but did not reduce it in rats with hypertension (facilitation of the action of the catecholamine on the mechanisms of lipolysis). This phenomenon is examined in connection with the presence of initial changes in the function of the plasma membranes of the fat cells in hypertensive animals. Hypertrophy of the adrenal cortex and potentiation of corticosteroid secretion in these types of hypertension can therefore be regarded as a measure of compensation for disturbance of the function of the cell plasma membranes in the tissues of the internal milieu.Department of Pathomorphology, Central Research Laboratory, No. 4 Main Board, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR E. I. Chazov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 12, pp. 672–675, December, 1978.     

Differential responses of white adipose tissue and brown adipose tissue to caloric restriction in rats

Caloric restriction (CR) slows the aging process and extends longevity, but the exact underlying mechanisms remain debatable. It has recently been suggested that the beneficial action of CR may be mediated in part by adipose tissue remodeling. Mammals have two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT). In this study, proteome analysis using two-dimensional gel electrophoresis combined with MALDI-TOF MS, and subsequent analyses were performed on both WAT and BAT from 9-month-old male rats fed ad libitum or subjected to CR for 6 months. Our findings suggest that CR activates mitochondrial energy metabolism and fatty acid biosynthesis in WAT. It is likely that in CR animals WAT functions as an energy transducer from glucose to energy-dense lipid. In contrast, in BAT CR either had no effect on, or down-regulated, the mitochondrial electron transport chain, but enhanced fatty acid biosynthesis. This suggests that in CR animals BAT may change its function from an energy consuming system to an energy reservoir system. Based on our findings, we conclude that WAT and BAT cooperate to use energy effectively via a differential response of mitochondrial function to CR.     

Reduction of the β-cell component of pancreatic islets in spontaneously hypertensive rats

Summary A morphometric study of the pancreatic islets in young spontaneously hypertensive rats (SHR, Okamoto and Aoki Wistar strain) and in normotensive Wistar rats (NWR) of the same age revealed that the SHR (in prehypertensive and in early hypertensive stages) had a significantly smaller mass of islet tissue and that the number of islets in the SHR was reduced by half. The ratio between the total masses of the pancreatic islets for the NWR and the SHR at the prehypertensive and early hypertensive stages was found to be: 10.530.61, respectively. The mass of the islet tissue in the SHR was reduced at the expense of the -cell component of the islets. No morphologic differences were found in the acinous tissue, and the pancreas and body weights were the same in both experimental groups.The glucose tolerance test revealed reduced glucose utilization in the SHR, which may be due to a relative insufficiency of the insulin secretion by the islets upon rapid (i.v.) glucose lodaing. Reduced plasma insulin response to i.v. glucose loading and a reduced rate of insulin utilization were found in the SHR as compared with the NWR.The poor development of the -cell tissue may be attributed either to the specific effect of the enhanced catecholamine excretion or to a low insulin requirement of the cell tissue membranes (insulin targets) as a consequence of the membrane ion transport alteration in spontaneous hypertension.Dr. Yuvenaly V. Postnov, M.D., D.Sc., Head of the Department of PathomorphologyDr. Svetlana I. Gorkova, M.D., Cand.Sc., pathologistDr. Larisa P. Solovyova M.D. boichemistThe authors are grateful to Mrs. L. A. Petrunina, Mrs. I. A. Zohichareva, Miss G. A. Orlova, Mrs. W. I. Tsarkova, and Miss A. V. Shapilova for valuable technical assistance.     

Alterations in tissue concentration and gene expression of adrenomedullin in spontaneously hypertensive rats

In order to elucidate the role of adrenomedullin in hypertension, we have compared concentrations of immunoreactive rat adrenomedullin and adrenomedullin messenger RNA levels in tissues of 8-week-old spontaneously hypertensive rats (SHR) with those of age-matched Wistar-Kyoto rats (WKY). The adrenomedullin immunoreactivity concentrations in adrenal gland and cardiac atrium were significantly higher in SHR than in WKY. The adrenomedullin content of cardiac ventricle was also significantly higher in SHR than in WKY. The rat adrenomedullin messenger RNA levels in adrenal gland and heart of SHR were also higher than those of WKY. These results suggest that adrenomedullin participates in the mechanism to counteract the blood pressure elevation in SHR.     

Protein kinase C activity in brain tissue of spontaneously hypertensive rats

Central Research Laboratory, Ministry of Health of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 108, No. 7, pp. 42–44, July, 1989.     

高果糖膳食对大鼠脂肪组织肾素-血管紧张素系统的影响

目的:观察高果糖膳食对大鼠脂肪组织炎症及肾素-血管紧张素系统(renin-angiotensin system,RAS)的影响,探讨Toll样受体2(Toll-like receptor 2,TLR2)炎症信号通路在其中的作用。方法:16只SPF级雄性SD大鼠随机分为正常对照组、高果糖组、高果糖+si RNA阴性对照组及高果糖+TLR2-siRNA组,正常对照组以普通饲料喂养,高果糖组以含60%果糖饲料喂养,高果糖+TLR2-siRNA组和高果糖+si RNA阴性对照组大鼠另分别予以TLR2-siRNA和si RNA阴性对照转染。干预14周后,检测大鼠血尿酸水平,ELISA法检测血清白细胞介素6(interleukin-6,IL-6)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、血管紧张素原(angiotensinogen,AGT)和血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)的水平,称取腹部脂肪重量,免疫组化法检测脂肪组织巨噬细胞的浸润,realtime PCR法检测脂肪组织IL-6、TNF-α、单核细胞趋化蛋白1(monocyte chemoattractant protein-1,MCP-1)、AGT、血管紧张素转化酶1(angiotensin-converting enzyme 1,ACE1)、血管紧张素Ⅱ1型受体(angiotensinⅡtype 1 receptor,AT1R)和血管紧张素Ⅱ2型受体(angiotensinⅡtype 2 receptor,AT2R) m RNA表达,Western blot检测TLR2的蛋白表达。结果:与正常对照组比较,高果糖组大鼠血尿酸明显升高,腹部脂肪重量明显增加,血清IL-6、TNF-α、AGT和AngⅡ水平明显升高,脂肪组织巨噬细胞浸润数量明显增多,脂肪组织IL-6、TNF-α、MCP-1、AGT、ACE1、AT1R和AT2R的m RNA水平明显升高(P 0. 05);与高果糖组比较,高果糖+TLR2-siRNA组大鼠血尿酸及腹部脂肪重量无明显变化,TLR2蛋白表达显著减低,血清及脂肪组织炎症因子的m RNA水平显著降低,脂肪组织巨噬细胞浸润数量明显减少,血清AGT、AngⅡ及脂肪组织RAS信号通路相关因子的m RNA水平明显下调(P 0. 05)。结论:高果糖膳食上调脂肪组织RAS,其机制可能与TLR2炎症信号通路激活相关。     

自发性高血压大鼠勃起功能及海绵体形态结构的改变

目的：探讨自发性高血压大鼠(SHR)勃起功能的改变及其发病机理。方法：雄性 SHR 及同系 WKY 大鼠,夹尾法测量大鼠收缩压(SBP),皮下注射阿朴吗啡(APO)检测阴茎勃起功能,光镜及透射电镜观察海绵体形态结构的变化。结果：SHR 组及 WKY 组阴茎勃起次数分别为0．6±0．5和2．4±0．6,差异非常显著。光镜下 SHR 大鼠阴茎海绵体血窦、内皮细胞、平滑肌细胞分布杂乱,血管内皮细胞连续性破坏;其内皮细胞及平滑肌细胞超微结构线粒体退变、内质网扩张,糖原颗粒、吞饮小泡及微丝减少。还可见大量间质组织增生及微血管腔闭塞。结论：高血压严重影响阴茎勃起功能,海绵体组织超微结构的病理改变可能是自发性高血压大鼠勃起功能下降的机理之一。     

Activation of muscarinic M-3 receptor may decrease glucose uptake and lipolysis in adipose tissue of rats

Role of muscarinic receptor in the regulation of glucose uptake or lipolysis in adipose tissue remained unclear. In epididymal white adipose tissue (WAT) isolated from Wistar rats, we observed that acetylcholine (ACh) attenuated the insulin-stimulated glucose uptake and the release of glycerol from WAT in a concentration-dependent manner. Using the blockade of specific antagonists, both actions of ACh were characterized mainly due to an activation of M3 receptors. In the presence of various inhibitors for PLC–PKC pathway, ACh-decreased glucose uptake was also reversed. Taken together, these results suggest that muscarinic M3 receptor is involved in the regulation of glucose uptake and/or lipolysis in adipose tissue.     

Exhaustive exercise causes an anti-inflammatory effect in skeletal muscle and a pro-inflammatory effect in adipose tissue in rats

It is well known that exhaustive exercise increases serum and skeletal muscle IL-6 concentrations. However, the effect of exhaustive exercise on the concentrations of other cytokines in the muscle and in the adipose tissue is controversial. The purpose of this study was to evaluate the effect of exhaustive exercise on mRNA and protein expression of IL-10, TNF-α and IL-6 in different types of skeletal muscle (EDL, soleus) and in two different depots of white adipose tissue (mesenteric–MEAT and retroperitoneal–RPAT). Rats were killed by decapitation immediately (E0 group, n = 6), 2 (E2 group, n = 6) and 6 (E6 group, n = 6) hours after the exhaustion protocol, which consisted of running on a treadmill (approximately 70% VO_2max for 50 min and then subsequently at an elevated rate that increased at 1 m/min every minute, until exhaustion). The control group (C group, n = 6) was not subjected to exercise. Cytokine protein expression increased in EDL, soleus, MEAT and RPAT from all exercised groups, as detected by ELISA. EDL IL-10 and TNF-α expression was higher than that of the soleus. The IL-10/TNF-α ratio was increased in the skeletal muscle, especially in EDL, but it was found to be decreased in the adipose tissue. These results show that exhaustive exercise presents a different effect depending on the tissue which is analysed: in the muscle, it induces an anti-inflammatory effect, especially in type 2 fibres, while the pro-inflammatory effect prevails in adipose tissue, possibly contributing to increased lipolysis to provide energy for the exercising muscle.     

肥大细胞在脂肪组织中的生理与病理作用

脂肪组织可分为白色脂肪组织(white adipose tissue,WAT)与棕色脂肪组织(brown adipose tissue, BAT).WAT行使能量储存功能,将人体多余的能量以化学能形式储存,而BAT则具有产热功能,在寒冷等刺激下将化学能转化为热能,以维持体温.脂肪组织同时还具有内分泌功能,可分泌多种激素...