Effect of Arterial Blood Pressure Reduction on Renal Hemodynamics in the Developing Lamb

Aperia , A. and P. Herin . Effect of arterial blood pressure reduction on renal hernodynamics in the developing lamb. Acta physiol. scand. 1976. 98. 387–394. The relationship between pressure and flow in the kidney has been examined in 2–9 and 31–48 day old lambs. Renal blood flow (RBF), determined by the microsphere technique, and glomerular filtration rate (GFR) were first studied under control conditions. The abdominal aorta was then constricted above the renal arteries until the pressure ranged between 60 and 70 mmHg, i.e. just below the normal auto-regulatory range, and the hemodynamic recordings were repeated. During control conditions the arterial pressure was lower in the younger (93 mmHg) than in the older lambs (107 mmHg). During aortic constriction total RBF and GFR were reduced. In both age groups GFR was reduced out of proportion to RBF. The sodium excretion fell around 60% in both age groups. The fall in perfusion pressure resulted in a more pronounced blood flow reduction to the outer than to the inner cortical glomerular capillaries. This pressure-induced blood flow redistribution was found in both age groups. The consequences of the pronounced effect of reducing the perfusion pressure to 60–65 mmHg for the young lambs with their basally low arterial blood pressure are discussed.     

Tubular Sodium Reabsorption and the Regulation of Renal Hemodynamics. The Effect of Chlorothiazide on Renal Vascular Resistance

In hydropenic dogs under Nembutal anesthesia chlorotiazide, in parallell with its inhibition of distal tubular Na reabsorption, caused a marked increase in renal vascular resistance and a decrease in total renal blood flow and glomerular filtration rate. The renal vasoconstriction appeared to be both pre- and post-glomerular, since the glomerular filtration rate was reduced in proportion to the total renal blood flow. The vasoconstriction could not be abolished by sympathetic blockade (Dibenzylene). During ureteral obstruction, when formation of glomerular filtrate could be regarded as minimal despite of unimpaired renal blood flow, the vasoconstrictive response to chlorothiazide was much reduced. This excludes a direct constrictive effect of chlorothiazide on the renal vascular bed. The constrictive response of the renal vascular bed was found to be correlated with the inhibition of Na reabsorption rather than with increase in urine flow. The data are interpreted as supporting the hypothesis that Na transfer in the distal tubule is one important mechanism for controlling renal vascular tone. a control that may be mediated by the renin angiotensin system. It is further suggested that the important factor is the intracellular Na concentration in the first part of the distal tubule. lather than intratubular concentration as such at this site. Contrary to previous interpretation the present observations suggest that it is a decrease in Na transfer, rather than an increase, that is directly or indirectly involved.     

Renal Hemodynamics in the Perinatal Period

The perinatal changes in renal hemodynamics have been studied in lambs. Eleven of the lambs were exteriorized, but maintained on placental circulation (fetal lambs). Eight of the lambs were delivered with cesarean section and studied immediately after clamping of the cord (newborn lambs). Nine lambs were delivered spontaneously and studied during the first 9 days of life. Renal blood flow (RBF) was determined by the microsphere method using a sample drawn from the iliac artery as the reference flow. The filtering capacity of the nephrons was evaluated after ferrocyanide injection and dissection of the nephrons. Total RBF did not seem to change much at birth but increased in relation to kidney weight during the first postnatal week. Clamping of the cord did, however, result in a change in intrarenal blood flow distribution, so that in the newborn lambs relatively more of the blood flow was perfusing the outer cortical region. During the first postnatal week there was a slight, but insignificant further relative increase in outer cortical blood flow. The relative increase in outer cortical blood flow at birth was accompanied by an increased frequency of filtering superficial nephrons from 22 to 77 %. Practically all juxtamedullary nephrons were filtering before birth. Three days postnatally 98 % of the superficial and 100 % of the juxtamedullary nephrons were filtering.     

Tubular Sodium Reabsorption and the Regulation of Renal Hemodynamics. The Effect of Hypertonic Saline Infusion on Renal Vascular Resistance

The hemodynamic response following saline loading was found to differ from that induced by the saluretic agent, chlorothiazide, which causes vasoconstriction. When hypertonic NaCl was infused into the renal artery until a profuse sodium diuresis was obtained, and the infusion then interrupted, C_Na/C_In remained elevated for 60–80 min. During this period the renal vascular resistance did not change significantly and the glomerular filtration rate tended to rise as compared with the control periods. This is contrary to what has previouly been found during chlorothiazide administration, where renal vascular resistance was significantly correlated with C_Na/C_In. A hypertonic saline load blocks Na reabsorption in the proximal tubules, chlorothiazide mainly in the distal tubules. It was therefore concluded that it is a reduction of movement of Na into the distal tubule cells, specifically the macula densa, rather than the increased Na concentration of the distal tubular fluid that is responsible for the vasoconstrictive effect of chlorothiazide.     

肾动脉狭窄形态对其血流动力学的影响

目的 探讨肾动脉狭窄(renal artery stenosis,RAS)的形态学参数对其血流动力学的影响,为临床治疗提供理论参考.方法 创建理想化RAS模型,运用计算流体力学方法探讨狭窄面积、对称性、长度和形状改变对肾动脉血流动力学影响.结果 肾灌注、压降和壁面剪切力分布与狭窄面积显著相关.当狭窄面积从50％逐步增大...     

Renal Interstitial Hydrostatic Pressure and Urinary Sodium Excretion in Rats with Angiotensin-Converting Enzyme Inhibitor-Induced Papillary Atrophy

The importance of angiotensin type-1 (AT1) receptor stimulation during renal development has recently been established in both pharmacological and knockout models. We have previously reported irreversible and progressive papillary atrophy and a reduced baseline renal interstitial hydrostatic pressure (RIHP) after neonatal angiotensin-converting enzyme (ACE) inhibition. The aim of the present study was to investigate the consequences of these abnormalities on urinary sodium excretion during acute extracellular sodium loading. Rats were treated neonatally with enalapril (10 mg kg-1 day-1) or saline control from days 3 to 23 after birth. Urinary sodium excretion was assessed in relation to mean arterial pressure (MAP) and RIHP responses in adult anaesthetised rats during moderate (1.5 and 3 % body weight) and severe (9 % body weight) saline-induced volume expansion. Control rats responded to the moderate volume expansion by increasing MAP by 16 +/- 6 % and RIHP by 40 +/- 23 %, respectively. In neonatally enalapril-treated rats, however, MAP and RIHP remained unchanged and were associated with a smaller increase in sodium excretion (44 +/- 11 % of the total amount infused versus 71 +/- 16 % for controls, P < 0.05). In contrast, severe volume expansion resulted in marked pressure rises in both the enalapril-treated group (36 +/- 12 and 112 +/- 48 % of baseline for MAP and RIHP, respectively) and the control group (34 +/- 21 and 130 +/- 34 % of baseline for MAP and RIHP, respectively). Moreover, the increases in MAP and RIHP were associated with complete excretion of the severe sodium challenge within 60 min in both treatment groups. We conclude that a RIHP response appears to be a prerequisite for adequate urinary sodium excretion in this model of papillary atrophy. Hence, an intact renal medulla is not mandatory in the renal handling of sodium during extracellular loading.     

The Effect of Thorotrast® and Cortisone on Renal Cortical Fibrinolytic Activity in the Rabbit

Previous studies have shown that a single injection of endotoxin inhibits renal cortical fibrinolytic activity in the rabbit. This suggests that the initial injection of endotoxin may prepare for the generalized Shwartzman reaction by depletion of cortical fibrinolytic activity. A fibrin slide technic was used to determine whether Thorotrast® and cortisone prepare for the generalized Schwartzman reaction by a similar mechanism. Renal cortical fibrinolytic activity was inhibited following Thorotrast injection, but no inhibition could be detected following cortisone injection. This suggests that Thorotrast, like endotoxin, prepares for the generalized Shwartzman reaction by depletion of cortical fibrinolytic activity. Failure to demonstrate inhibition of lytic activity following cortisone injection may indicate that cortisone prepares for the generalized Shwartzman reaction by another mechanism, or that the fibrin slide technic was unable to detect quantitative changes in lytic activity.     

肾间质纤维化中MicroRNA表达研究进展

MicroRNA (miRNA)是一种高度保守、内源性的非编码小分子RNA,主要参与生物体中转录后水平基因表达的调控.miRNAs在各种肾脏疾病的发病机制中起重要作用.肾间质纤维化是各种慢性肾脏病进展至终末期,最终导致器官功能丢失的共同的病理过程和特征.转化生长因子β(TGF-β)在肾纤维化过程中是公认的一个重要的介质,它能刺激细胞外基质(ECM)的积聚并损害肾功能.近年研究发现,在肾脏组织中存在的一些miRNAs对肾脏纤维化的发生与发展有着重要的作用,深入地了解它们之间的关系可以为临床肾脏纤维化的治疗提供新的治疗靶点.     

组织间隙氧分压的数值模拟及统计分析

研究如何通过测量组织间隙离散点的氧分压来进行局部组织的氧供应情况分析,以及进行机体相关参数分析。基于组织氧扩散的圆柱模型,利用Matlab软件,对单根、双根同血流及异血流方向血管和多根同血流方向血管周围组织中的氧分压分布进行数值仿真,并用统计分析方法对数值模拟结果进行频率分析。理论模拟组织氧分压的概率分布规律与动物实验结果很相似,并且可以得到组织间隙氧分压的概率分布与单根血管的供氧区域(R)和组织间隙氧扩散系数(K)的定量关系。理论研究证实,可以通过测量组织间隙离散点的氧分压来描述局部组织的氧供应情况,为临床确定局部组织供血情况和组织间隙氧扩散系数提供一个有效方法。     

大黄蟅虫超微粉剂对大鼠肾间质纤维化的影响

目的比较大黄蟅虫传统丸剂与超微粉剂对肾间质纤维化大鼠模型的药效作用。方法实验动物分为假手术组、模型组、传统丸剂组（0．54g／kg／d）、超微粉剂组（0．27g／kg／d）4组。采用单侧输尿管结扎的方法复制大鼠肾间质纤维化模型,用大黄蟅虫传统丸剂与超微粉剂进行干预,观察不同剂型对肾间质纤维化大鼠肾功能指标、血清纤维化指标、病理组织变化的影响。结果与假手术组相比,模型组血清肌酐（Cr）、尿素氮（Urea）、透明质酸（HA）、层黏蛋白（LN）、Ⅳ型胶原（IV—C）、Ⅲ型前胶原（PCⅢ）显著升高（P〈0．01）,肾间质纤维化明显。与模型组相比,大黄蟅虫传统丸剂组与超微粉剂组血清Cr、Urea、HA、LN、PCⅢ、Ⅳ—C降低（P〈0．01）,肾小管损害和肾间质纤维化程度减轻。与传统丸剂组相比,超微粉剂组血清Cr、Urea较低（P〈0．05）,其余指标差异无统计学意义。结论大黄蟅虫传统丸剂与超微粉剂对实验性肾间质纤维化都有较好的防治作用,能降低肾间质纤维化程度。改善肾功能;在改善肾功能方面,超微粉剂型优于传统丸剂型。复方“大黄蟅虫”药材超微粉碎后减少药量的同时有助于提高药效,有利于剂型现代化。     

螺内酯对马兜铃酸所致大鼠肾间质纤维化防治作用的研究

目的探讨螺内酯对马兜铃酸(Aristolochic Acid,AA)所致大鼠肾间质纤维化的防治.方法大白鼠随机分成3组,正常对照组、木通组、木通螺内酯组.在实验前及实验的第2、4周,分别从各组大鼠眼内眦静脉采血,测定血肌酐(SCr)、血尿素氮(BUN)、血钾、血钠等生化指标以及Ⅲ型前胶原(PC Ⅲ)、血清透明质酸(HA)、层粘连蛋白(LN)等放免指标,42d时从心脏直接采血复查上述各指标,而后处死动物取肾脏进行组织形态学及特殊染色检查.结果1、木通螺内酯组和木通组用药前后自身比较血生化、放免指标有统计学意义.2、木通螺内酯组和木通组用药后组间比较血生化、放免指标有统计学意义.3、木通螺内酯组和木通组用药后组间比较免疫组化指标有统计学意义.结论1、醛固酮抑制对AA所致的慢性肾间质纤维化有一定的防治作用.2、在AA所致的慢性肾间质损伤时血电解质紊乱以钾、钠表现为明显,血氯和血钙变化不明显.3、血放免指标PC Ⅲ、HA、LN可以作为早期慢性肾间质纤维化的重要临床观察指标.     

肾综合征出血热若干体液因子和肾脏血液动力学变化的关系

研究了２８例肾综合征出血热（ＨＦＲＳ）患者体液因子和肾脏血液动力学的变化。用放射免疫法检测了血浆内皮素（ＥＴ）、Ｐ物质（ＳＰ）、血栓素Ｂ２（ＴＸＢ２）、６－酮－前列腺素Ｆ１α（６－ｋ－ＰＧＦ１α）及血管紧张素－Ⅱ（ＡＴ－Ⅱ）的含量，用放射性核素计算机扫描成像摄影法（ＥＣＴ）测定了肾小球滤过率（ＧＦＲ）和肾有效血浆流量（ＥＲＰＦ），结果发现，ＨＦＲＳ患者从发热期至多尿初期血浆ＥＴ、ＴＸＢ２、ＡＴ－Ⅱ均高于正常水平，而血浆ＳＰ则低于正常水平，６－Ｋ－ＰＧＦ１α除低血压少尿期外其他各期亦都低于正常。ＧＦＲ与ＥＲＰＦ从发热后期至多尿期均明显下降，及至恢复初期多数重型患者仍未恢复正常。上述结果提示体液因子的平衡失调是造成内脏缺血和急性肾功能衰竭的重要因素，如采取适当措施抑制编血管物质的强烈作用，则有利于循环的恢复。     

Renal Cortical Blood Redistribution after Bumetanide Related to Heterogenicity of Cortical Prostaglandin Metabolism in Dogs

Bumetanide is shown to increase renal blood flow and to augment the proportion of the cortical blood flow to middle cortex. This redistribution still takes place even when renal blood flow is maintained constant by renal artery clamping. Indomethacin pretreatment inhibits the increase of renal blood flow as well as the cortical blood redistribution. In vitro examinations of canine kidney tissue slices suggest that outer cortex and papilla are sites of prostaglandin synthesis. No differences in prostaglandin E degradation are observed within the cortex. This suggests a relative autonomy for prostaglandins in the outer cortex, whilst inner cortical areas are dependent on medullary/papillary prostaglandin E supply. The renal hemodynamic effect of bumetanide is therefore thought to be a result of a stimulation of mainly medullary/papillary prostaglandin synthesis.     

赛庚啶对大鼠垂体-肾上腺皮质轴的作用观察

目的　研究赛庚啶 (cyproheptadine ,CYP)对大鼠垂体、肾上腺皮质超微结构的影响。 方法　用透射电子显微镜观察经 4 6mg/kg/d赛庚啶灌胃后垂体、肾上腺皮质超微结构的改变。结果　实验组大鼠肾上腺皮质束状带细胞线粒体结构不清 ,异染色质边集 ,核周隙明显增宽 ,细胞核固缩 ,出现退行性改变。垂体促肾上腺皮质激素细胞线粒体嵴肿胀、断裂 ,出现髓样变 ,粗面内质网脱颗粒 ,胞浆内分泌颗粒明显减少。结论　赛庚啶对大鼠垂体、肾上腺皮质超微结构产生明显影响     

Mucosal Hemodynamics in the Small Intestine of the Cat during Reduced Perfusion Pressure

This study was performed with an indicator-dilution technique that allowed quantitative and separate investigation on the cat small intestine, of the “mucosal” as well as of the “villous” intravascular flows and volumes. When reducing arterial inflow pressure from about 100 to about 30 mm Hg “villous” plasma volume and mean transit time increased while “villous” plasma flow remained largely unaltered. Concomitantly, total intestinal blood flow decreased significantly indicating that a larger fraction of total plasma flow was diverted to the villi at low inflow pressure. When intestinal blood flow was reduced by increasing venous outflow pressure villous hemodynamics was largely unaffected. “Mucosal” red cell and plasma flows were affected in the direction of and, generally speaking, in proportion to total intestinal blood flow. These results suggest that the autoregulatory capacity of the villous vessels is larger than that of the vessels in the deeper parts of the mucosa.     

Hemodynamics of Blood Pressure Responses During Active and Passive Coping

This laboratory study was designed to address a number of interrelated issues regarding cardiovascular reactivity to psychological stress. One objective was to extend the previous research comparing cardiovascular responses during active versus passive coping, by comparing responses to two task conditions designed to be similar in all ways except the opportunity to make a response influencing the task's outcome. A second objective was to compare responses to two different passive film tasks, which differed in outcome uncertainty and the degree of vicarious active coping achieved through identification with the role portrayed by the actors. A third objective was to evaluate whether individuals are predisposed to exhibit a particular hemodynamic pattern underlying their blood pressure adjustments, independently of the task demands imposed. Ninety healthy young adult male subjects were tested in pairs on a series of tasks that included a competitive reaction-time task, an active as well as a passive phase of a team reaction-time task, and passive viewing of two film segments. The tasks demanding active coping responses tended to raise blood pressure due primarily to an increase in cardiac output, while vascular resistance fell. During passive coping demands cardiac output increased to a lesser extent, but vascular resistance also tended to increase, thereby raising blood pressure by their synergistic effects. However, these patterns were not typical of all participating subjects. On the basis of their cardiac output and vascular resistance responses to the competitive reaction-time task, one third of the subjects were categorized as being high myocardial reactors (n = 30) and another third high vascular reactors (n = 31). Post-hoc analyses of responses to the other tasks, based on these categorizations, indicated that the hemodynamic basis of reactivity is an individual characteristic only partially modified by coping demands. The active/passive coping dimension is discussed both conceptually and in relation to the role of stress in the etiology of hypertension.     

Effect of Sildenafil on Neuropathic Pain and Hemodynamics in Rats

Purpose

The inhibition of phosphodiesterase 5 produces an antinociception through the increase of cyclic guanosine monophosphate (cGMP), and increasing cGMP levels enhance the release of γ-aminobutyric acid (GABA). Furthermore, this phosphodiesterase 5 plays a pivotal role in the regulation of the vasodilatation associated to cGMP. In this work, we examined the contribution of GABA receptors to the effect of sildenafil, a phosphodiesterase 5 inhibitor, in a neuropathic pain rat, and assessed the hemodynamic effect of sildenafil in normal rats.

Materials and Methods

Neuropathic pain was induced by ligation of L5/6 spinal nerves in Sprague-Dawley male rats. After observing the effect of intravenous sildenafil on neuropathic pain, GABAA receptor antagonist (bicuculline) and GABAB receptor antagonist (saclofen) were administered prior to delivery of sildenafil to determine the role of GABA receptors in the activity of sildenafil. For hemodynamic measurements, catheters were inserted into the tail artery. Mean arterial pressure (MAP) and heart rate (HR) were measured over 60 min following administration of sildenafil.

Results

Intravenous sildenafil dose-dependently increased the withdrawal threshold to the von Frey filament application in the ligated paw. Intravenous bicuculline and saclofen reversed the antinociception of sildenafil. Intravenous sildenafil increased the magnitude of MAP reduction at the maximal dosage, but it did not affect HR response.

Conclusion

These results suggest that sildenafil is active in causing neuropathic pain. Both GABAA and GABAB receptors are involved in the antinociceptive effect of sildenafil. Additionally, intravenous sildenafil reduces MAP without affecting HR.