Cardiovascular Control in the Milan Strain of Spontaneously Hypertensive Rat (MHS) at “Rest” and during Acute Mental “Stress”

The cardiovascular responses to acute mental “stress” were compared in the Milan strain of spontaneously hypertensive rats (MHS) and in normotensive control rats (NR). Blood pressure and heart rate were followed in pairs of awake MHS and NR, while defence reactions were provoked by alerting stimuli (noise, vibration). No differences were noted between the two groups in response to “stress” although resting heart rate in MHS was lower than in NR. Administration of atropine or propranolol to MHS and NR showed the MHS to have a higher resting vagal tone and lower sympathetic tone than the NR. Subsequent (at least two weeks later) hemodynamic investigation, under nembutal anesthesia, showed no difference in cardiac output between MHS and NR but a higher stroke volume, presumably related to the lower heart rate in MHS. Thus, total peripheral resistance was increased in MHS as was the ratio left ventricular weight/body weight, and in good proportion to the blood pressure rise. Thus MHS differ substantially in both their responses to “stress” and also hemodynamically from the Okamoto strain of spontaneously hypertensive rat (SHR), being the so far most studied and best known model of essential hypertension in man. In MHS the hypertension is more of a systolic type and is of primarily renal origin. As such, MHS provide another model for investigating the polygenic nature of hypertension in man.     

Capillary Permeability to Albumin in Normotensive and Spontaneously Hypertensive Rats

Transcapillary passage of plasma proteins is enhanced in man's primary hypertension and it is debated whether this reflects increased permeability or merely a raised capillary pressure. To elucidate this problem, maximally vasodilated hindquarters of spontaneously hypertensive rats (SHR) and normotensive controls (NCR) were perfused in parallel at constant flow with dextran, horse serum or mixtures of the two, using labelled albumin as indicator of capillary permeability to macromolecules. By equal increases of venous pressure modest filtration was maintained during one hour, after which the edema and its albumin content were determined. — There was less edema in SHR, reflecting a slightly lower postcapillary resistance and a much higher precapillary resistance compared with NCR, which here resulted in a lower capillary pressure in SHR. In both SHR and NCR the presence of dextran slightly enhanced the capillary filtration coefficient but increased albumin permeability up to tenfold, also after antihistamine drugs. However, for each perfusate the SHR capillaries were, if anything, slightly less permeable to albumin than the NCR ones. — The results suggest that the enhanced transcapillary passage of plasma proteins in primary hypertension reflects an increased capillary pressure in some circuit(s), probably mainly skeletal muscle, resulting from the functional balance in vivo between the pre- and postcapillary resistances.     

自发性高血压大鼠淋巴微循环功能受损

目的:观察自发性高血压大鼠(SHRs)淋巴微循环功能变化.方法:8周龄雄性SHR大鼠(SHR组)和WKY大鼠(WKY组),每组各10只.应用VasT rack测量两组大鼠微淋巴管自律运动;取胸导管分离原代淋巴管内皮细胞(LECs).应用免疫荧光和Western Blot检测LECs血管内皮生长因子受体3(VEGFR3)...     

Consequence of Social Isolation on Blood Pressure,Cardiovascular Reactivity and Design in Spontaneously Hypertensive Rats

Spontaneously hypertensive rats (SHR), which inherently display exaggerated cardiovascular defence reactions to environmental stimuli (Hallbäck and Folkow 1974), and normotensive control rats (NCR) were kept isolated after they were weaned to reduce such environmental influences which normally induce psychological activation. Mean arterial pressure was followed until 7 months of age, when the cardiovascular defence reactions to acute mental stress were compared and an analysis of cardiovascular design was made. The isolated SHR but not the isolated NCR, had significantly lower pressures than their unisolated controls. Likewise, judged by the relative weight of the left ventricle and the hemodynamically evaluated design of the hindquarter resistance vessels, the structural cardiovascular adaptation was about proportionally less pronounced in isolated than in control SHR. However, their cardiovascular responses to acute “psychological stress” were equally intense, and clearly exaggerated when compared with NCR. Thus, a prolonged reduction of excitatory environmental influences implies a relatively less pronounced development of hypertension in SHR, even though an inherent hyperreactivity concerning neurohormonal pressor responses to alerting stimuli is present. These findings stress the importance of interacting intrinsic-hereditary and extrinsic neurogenic influences for the initiation of primary hypertension.     

自发性高血压大鼠肾动脉的零应力状态

通过观察动脉主干张开角的大小,研究了自发性高血压大鼠（Ｓｐｏｎｔａｎｅｏｕｓｌｙ ｈｙｐｅｒｔｅｎｓｉｖｅ,ｒａｔ,ＳＨＲ）高血压建立后肾动脉零应力状态的变化,并于ＳＨＲ高血压形成前,分别给予口服型ＡｎｇⅡ Ⅰ型受体拮抗剂Ｌｏｓａｒｔａｎ和ＥＴ Ａ型受体拮抗剂ＢＭＳ－１８２８７４,研究内源性ＡｎｇⅡ和ＥＴ在ＳＨＲ肾动脉零应力状态变化中的作用。 现,在高血压已建立的ＳＨＲ,肾动脉主干张开角（１１４．     

Acute Immune and Non-Immune Inflammatory Response in Spontaneously Hypertensive Rats and Normotensive Rats. Role of Endogenous Nitric Oxide

Summary The present study investigated the acute inflammatory response (increase in vascular permeability and leukocytes migration) in the pleura of spontaneously hypertensive rats (SHR) and normotensive rats (NTR), using two different stimulus: carrageenan and active anaphylaxis. In addition, the role of endogenous nitric oxide in these responses was investigated. Results The inflammatory response induced by intrapleural carrageenan injection in SHR developed similarly to that in NTR. Treatment with L-NAME, reduced the intensity of this response in both groups of rats. The inflammatory response induced by active anaphylaxis in SHR and NTR was different. The increase in vascular permeability occurred later in the SHR compared to NTR. The number of leukocyte present in inflammatory exudates was increased at 4 h in both groups of rats. L-NAME treatment did not inhibit exudation at the intervals under analysis, however, reduced the number of mononuclear cells in the inflammatory exudate of SHR. Conclusion The development of the inflammatory response in SHR differs from that in NTR, depending on the nature of the inflammatory stimulus. Endogenous NO plays a clear role in carrageenan-induced inflamma-tion, but not in immunologically mediated inflammation in the analyzed period.     

Dimethylarginines and Serotonin in the Blood of Spontaneously Hypertensive Rats

The serotoninergic system and nitric oxide system were studied in spontaneously hypertensive rats SHR and Wistar rats (control). The contents of serotonin, 5-hydroxyindoleacetic acid (serotonin metabolite), L-arginine, monomethylarginine, and asymmetric and symmetric dimethylarginines were measured in blood plasma. Serotonin content in hypertensive animals was much higher than in Wistar rats. No interstrain differences were found in the concentration of 5-hydroxyindoleacetic acid. The concentration of asymmetric dimethylarginine in SHR rats was higher than in Wistar rats. However, the concentration of monomethylarginine in SHR rats was lower than in Wistar rats. Our results and published data on the serotoninergic system indicate that SHR rats serve as a convenient model of hypertension.     

Structural “Resetting” of the Renal Vascular Bed in Spontaneously Hypertensive Rats (SHR)

Studies in both man and rats (cf. Folkow et al. 1973, 1974) show that a rapid structural adaptation occurs early in hypertension which, besides the left heart and systemic arteries, affects the precapillary resistance vessels in a hemodynamically most important way. Here a wall (mainly media) thickening takes place which tends to encroach upon the inner radius, thus raising the w/r_i ratio. The rapidity, generalization and extent of this precapillary ‘“structural autoregulation” to average changes in pressure load makes it crucial both for the initiation and maintenance of a chronic high-pressure state, whichever the initiating elements are. The same principle of hypertrophic adaptation in the left heart and large arteries leads to a functionally important displacement of the “Starling curve” towards the right (Hallbäck, Isaksson and Noresson 1975) and to baroreceptor resetting (e.g. Jones 1977).     

Effects of Prolonged Treatment with Adrenergic β-receptor Antagonists on Blood Pressure,Cardiovascular Design and Reactivity in Spontaneously Hypertensive Rats (SHR)

Young “prehypertensive” SHR were treated with two kinds of β-adrenergic receptor antagonists from 2 1 / 2 up to 8 months of age. Arterial pressure largely remained at prehypertensive levels and acute cardiovascular responses to “stress” were considerably modified compared to untreated SHR. Quantitative hemodynamic analyses revealed that resistance vessel design exhibited only slight hypertensive changes when related to untreated controls, while the development of left ventricular hypertrophy was far less influenced by the treatment. In part of the group, pressure was followed for another 6 months after treatment, showing only a delayed and modest pressure rise compared with untreated, matched SHR. When instead adult SHR, with “established” hypertension, were similarly treated from 8 up to 10 months of age, resting arterial pressure remained unaffected and the resistance vessels exhibited only modest regression of the hypertensive changes, with signs of a largely preserved increase of vascular wall/lumen ratio, and with negligible regression of cardiac hypertrophy. The results indicate that early, “preventive” treatment of SHR with β-receptor blockers is of considerable value whichever their exact modes of action, though some regression of vascular changes can be achieved also in established hypertension, particularly in females (Weiss 1974).     

自发性高血压大鼠胸主动脉的

选取自发性高血压大鼠SHR在高血压形成前后的不同时相点,采用组织形态学方法结合计算机图像分析,对SHR大鼠胸主动脉几何形态及纤维结构进行了形态定量学研究,测定了SHR胸主动脉零应力状态张开角的变化及压力-直径关系。结果表明,随着血压增高,SHR主动脉几何形态及各种显微结构指标均显著增大;高血压形成和发展阶段,SHR主动脉零应力状态张开角增大;高血压主动脉结构重建例如管壁增厚,胶原纤维不成比例地增加可能导致主动脉可扩张性降低;主动脉的结构重建和力学特性的改变构成了高血压心血管并发症的重要基础。     

Comparison of the Somatosympathetic Reflex in Normotensive and Spontaneously Hypertensive Rats

Acute experiments under chloralose anaesthesia were performed in normotensive (Wistar and Wistar-Kyoto) and hypertensive (SHR) rats for recording of electrical discharge in the upper cervical sympathetic stem in response to stimulation of afferent fibers of the median nerve of the forelimb. These experiments showed that the evoked response was of the same shape in hypertensive rats as in normotensive rats. The latent period, duration of each discharge, and spectral characteristics of the somatosympathetic reflex were identical in animals of all the lines studied, though the amplitude of the reflex was greater in SHR rats than in normotensive animals. It is suggested that the organization of the somatosympathetic reflex is identical in hypertensive and normotensive rats. The reflex excitability of the sympathetic nervous system was increased in SHR rats.     

阿托伐他汀对高血压大鼠肾脏CTGF表达的影响

目的:观察自发性高血压大鼠(SHR)肾脏结缔组织生长因子(CTGF)的表达,探讨3-羟基-3-甲基戊二酞辅酶A(HMG-CoA)还原酶抑制剂阿托伐他汀(Atorvastin)对高血压肾损害的保护作用。方法:20只12周龄雄性SHR随机分为阳性对照组和阿托伐他汀干预组各10只,药物干预组每只大鼠予以阿托伐他汀20mg/kg/天灌胃(共12周);10只12周龄雄性WKY大鼠作为正常对照组。测量不同时期各组大鼠尾动脉收缩压(SBP)、血脂、尿β2-微球蛋白(β2-MG)及肾功能指标;用免疫组织化学方法检测CTGF蛋白在各组大鼠肾脏中的表达;用RT-PCR方法检测CTGFmRNA在肾脏的表达水平。结果:⑴与正常对照组、药物干预组相比,阳性对照组血清尿素氮(BUN)、肌酐(Cr)水平无显著差异,而SBP、血脂、尿β2-MG均显著增高(P<0.01)。⑵CTGF蛋白及mRNA在阳性对照组肾脏中的表达较正常对照组明显增强,药物干预组比阳性对照组明显减少(P<0.05)。结论:CTGF表达增加可能是导致高血压肾损害的重要机制之一;阿托伐他汀通过降低血压及血脂,显著减少尿β2-MG,改善肾组织的病理变化,抑制CTGF在SHR肾脏表达而发挥对高血压肾损害的保护作用。     

自发性高血压大鼠胸主动脉的结构重建及力学特性

选取自发性高血压大鼠ＳＨＲ在高血压形成前后的不同时相点,采用组织形态学方法结合计算机图像分析,对ＳＨＲ大鼠胸主动脉几何形态及纤维结构进行了形态定量学研究,测定了ＳＨＲ胸主动脉零应力状态张开角的变化及压力－直径关系。结果表明,随着血压增高,ＳＨＲ主动脉几何形态及各种显微结构指标均显著增大;高血压形成和发展阶段,ＳＨＲ主动脉零应力状态张开角增大;高血压主动脉结构重建例如管壁增厚,胶原纤维不成比例地增加     

卡托普利对自发性高血压大鼠微血管稀少和内皮功能障碍的影响

为探讨自发性高血压大鼠（SHR）的微血管改变和血管内皮细胞（VEC）功能障碍的关系及卡托普利（CPT）的干预效果，对9只SHR给予CPT（CPT组），并以10只WKY大鼠作为正常对照组（WKY组），以10只SHR作为实验纠（SHR组），观察检测人鼠的血压（BP）、回肠壁各级微动脉分支总数、血浆一氧化氮（NO）和血浆内皮素（ET）。结果显示，SHR组的微动脉分支总数、NO及K值[log(NO／ET)]均较WKY组下降（P均<0.01），而ET则增高（P＜0．01）；CPT组给药后第7口BP较给药前下降（P<0．01），其微动脉分支总数、NO及K值均较SHR组增加（P均<0．01）；SHR的BP与K值呈负相关（r=－0．5863），BP与各级微动脉分支总数呈负相关(r＝－0．7866～－0．6380），而K值与各级微动脉分支总数呈正相关（r＝0.5951～0.7529）。认为SHR的微血管改变与其内皮功能状态关系密切，CPT时改善高血压的VEC功能和微血管稀少现象，从而发挥降压作用。     

自发性高血压大鼠肾脏和胰腺微循环血流灌注和自律运动变化

目的:观察自发性高血压大鼠(SHRs)肾脏和胰腺微循环血流灌注和自律运动变化。方法:市购8周龄SHRs(SHR组)和正常血压对照大鼠(WKY组)各6只,手术暴露肾脏和胰腺。采用双通道激光多普勒血流仪,多点观测其表面的微血流灌注和自律运动水平,并通过仪器自带分析软件的小波变换功能将微血流信号转换为二维频谱图和三维时频图像,比较两组大鼠肾脏、胰腺血流灌注水平、血流速度和血细胞浓度的变化特征及微血流灌注频谱中一氧化氮(NO)依赖与否的内皮细胞源频段幅值差异。结果:与WKY组相比,SHR组肾脏、胰腺微血流灌注水平均显著降低(P<0.05或P<0.01);同时呈现胰腺微血管自律运动节律紊乱。SHR组肾脏和胰腺微血管自律运动振幅和频率均显著降低(P<0.05或P<0.01)。SHR组肾脏和胰腺微血流灌注频谱中NO依赖与否的内皮细胞源频段振幅均显著低于WKY组(P<0.05或P<0.01)。结论:SHRs肾脏、胰腺微循环功能异常,表现为微血流灌注水平下降,微血管自律运动功能障碍。     

开博通与左旋精氨酸对自发性高血压大鼠血管内皮细胞功能的影响

观察开博通(CPT)和左旋精氨酸(L-Arg)对自发性高血压大鼠(SHR)血管内皮细胞功能影响 ,探索两者联合使用的降压机制。方法Wastar大鼠10只作正常对照组。另38只SHR随机分为SHR对照组(n=10),L_Arg治疗组(n=10),CPT治疗组(n=9),L_Arg和CPT联合治疗组(n=9)。同时测各组用药前后的血压 ,一氧化氮(NO)和内皮素(ET)。结果SHR组的NO低于正常对照组而ET则高于对照组(P<0.05) ,L_Arg和/或CPT两治疗组的NO和ET各有不同程度升高和降低 ,(与SHR组比较均P<0.05) ,其中以L—Arg CPT联合治疗组最明显。3个治疗组用药后血压较用药前均有不同程度的下降(均P<0.001) ,而又以L—Arg CPT联合组降压效果最佳。结论CPT和L_Arg均可有效增加SHR的NO合成释放 ,加强CPT降压效应     

卡维地洛对高血压大鼠主动脉的保护作用

目的 :研究卡维地洛对核因子 κB(NF κB)、单核细胞趋化蛋白 1(MCP 1)在自发性高血压大鼠 (SHR)大血管中表达的影响 ,探讨其对血管保护的机制。方法 :18只雄性 12周龄SHR随机分为阳性组 ,卡维地洛组 ( 30mg/kg·d) ,美托洛尔组 ( 50mg/kg·d) ,灌喂 8周 ;另选同龄雄性WistarKyoto大鼠为阴性组 (n =6 )。用免疫组化法测各组主动脉NF κB、MCP 1的表达 ,ELISA法测血清MCP 1含量。结果 :与阴性组比较 ,阳性组主动脉组织中NF κB、MCP 1表达增加 (P<0 .0 1) ,且两者正相关 (r=0 .72 8,P <0 .0 1) ;血清MCP 1含量升高 1.6 4(P <0 .0 1)。 8周后 ,治疗组之间血压无明显差异 (P >0 .0 5) ,但卡维地洛更显著抑制NF -κB、MCP 1表达 (P <0 .0 5)。结论 :卡维地洛可能独立于降压外抑制NF κB的活化来调控MCP 1表达。     

The Effects of “Immunosympathectomy” on Blood Pressure and Vascular “Reactivity” in Normal and Spontaneously Hypertensive Rats

Newborn litters of spontaneously hypertensive rats (SHR) and normotensive control rats (NCR) were identically treated with sympathetic nerve growth factor antiserum (Wellcome) which markedly interferes with adrenergic cardiovascular control (Zaimis 1967). Blood pressure, measured intermittently during 8 months, was in treated SHR (SHR_is) about 25 % higher than in NCR_is, their respective pressures being about 40 % and 25 % lower than those of sham-treated SHR and NCR.–The hindquarters of one SHR_is, or NCR_is, were then perfused at constant flow in parallel with those of ordinary NCR. Starting from maximal vasodilatation, resistance increases were induced by graded noradrenaline (NA) infusions, from “threshold” to maximal pressor responses. Compared to NCR_is, SHR_is showed an increased resistance at maximal dilatation, an increased slope of the NA dose-response curve and an increased maximal pressor response, while their NA “thresholds” did not differ significantly. Thus, the structurally determined hemodynamic differences between ordinary SHR and NCR (Folkow et al. 1970 b) characterize also SHR_is and NCR_is, though to a reduced extent. Even when comparing SHR_is with ordinary- NCR, which exhibited similar “resting” pressures, these differences partly remain, suggesting that the SHR resistance vessels might, for genetic reasons, be more prone to adapt structurally to pressure loads than those of NCR.