Is the cortical capillary renamed as the transcortical vessel in diaphyseal vascularity?

A recent article published in Nature Metabolism, “A network of trans-cortical capillaries as a mainstay for blood circulation in long bones,” explained the long bone vascularity. In the mouse model, the authors demonstrated hundreds of transcortical vessels (TCVs) commencing from the bone marrow and traversing the whole cortical thickness. They realized that TCVs were the same as bleeding vessels of periosteal bed observed in the human tibia and femoral epiphysis during surgery. TCVs expressed arterial or venous markers and were proposed to be the backbone of bone vascularity as 80% of arterial and 59% of venous blood distributed through them. This new evidence challenged the existence of the “cortical capillaries” stated in previous literature. We conducted a review of the existing literature to compare this model with those in earlier research. The bone vascularity model was explained by many researchers who did their work in animal models like pig, dog, rabbit, and mouse. The TCVs were identified in these animal model studies as cortical capillaries or vessels of cortical canals. Studies are scarce, showing the presence of TCVs in humans. The role of TCVs in human cortical vascularity remains ambiguous until the substantial evidence is collected in future studies.     

Myoendothelial contacts in arteriolosclerosis.

Human renal biopsies were examined electron microscopically to investigate close contacts between endothelial and smooth muscle cells in small arterioles. These myoendothelial contacts were seen in the form of cytoplasmic projections passing through fenestrae in the basal lamina. Most of these cell processes seem to arise from the endothelial cells. In the control vessels, the separation between the endothelial cells and smooth muscle cells of the tunica media is 0.09-0.27 microns. With arteriolosclerosis there is an increasing separation between the elements of the intima and the media, from 1.0 to 2.42 microns. In spite of this increasing separation, myoendothelial contacts maintain an intercellular space of 10-15 nm, as observed in the control vessels. At 2.42 microns of separation, the amount of extracellular material accumulated is such that the cells can no longer keep in contact. Break up of the myoendothelial contacts may be responsible for impairment of communication between the tunica intima and media in the vessel wall in arteriolosclerosis.     

正常高值血压人群微量白蛋白尿和小动脉顺应性的变化

目的研究正常高值血压和理想血压人群中微量白蛋白尿和小动脉顺应性(C2)的变化及其影响因素。方法入选正常血压受试者153例,分成两组:理想血压组(n=53)和正常高值血压组(n=100)。检测腰围、身高、体重、坐位血压,晨起静脉空腹血糖、血脂、肝肾功能,尿液肌酐等指标;放射免疫法检测尿液微量白蛋白,计算尿液微量白蛋白与肌酐比(ACR);用HDI CVprofilorDO-2020检测大小动脉顺应性。结果理想血压组和正常高值血压组收缩压、舒张压、脉压和C2、ACR均有明显差异(P<0.05);相关分析显示,收缩压与log C2呈负相关(r=-0.439,P<0.001),与log ACR正相关(r=0.460,P<0.001);log ACR与log C2之间也有明显负相关性(r=-0.461,P<0.001);多元回归分析发现,收缩压是独立影响微量白蛋白尿和C2的指标。结论随血压水平的上升,C2逐渐降低,微量白蛋白尿水平逐渐提高,其水平的提高能一定程度上反映C2的减退;收缩压是影响正常高值血压人群微量白蛋白尿和C2的独立因素。     

ROLE OF NITRIC OXIDE IN THE CONTROL OF GLOMERULAR MICROCIRCULATINO

1. Nitric oxide (NO) plays an important role in the control of glomerular haemodynamics and is synthesized from the amino acid L-arginine by a family of enzymes, NO synthase (NOS). 2. Nitric oxide synthase is present in the endothelium and also in the macula densa, a plaque of specialized tubular epithelial cells. Endothelial NOS is known to be stimulated by shear stress and hormones, while the factor that regulates the activity of macula densa NOS remains undefined. 3. Studies with the in vitro microperfusion of glomerular arterioles have shown that the constriction of afferent arterioles (Af-Art) induced by myogenic responses and angiotensin II (AngII) is stronger in the absence rather than in the presence of luminal flow. Furthermore, endothelial disruption or NOS inhibition abolishes such differences, suggesting that flow through the lumen stimulates the endothelium to synthesize and release NO, which in turn attenuates both the myogenic response and the action of AngII in the Af-Art. 4. In contrast, NOS inhibitors have no effect on efferent arteriolar (Ef-Art) constriction induced by AngII. 5. In preparations in which Af-Art and the macula densa are simultaneously microperfused, selective inhibition of macula densa NOS has been shown to augment Af-Art constriction when the NaCl concentration at the macula densa is high, suggesting that the macula densa produces NO, which in turn modulates tubuloglomerular feedback. 6. Thus, the differential actions of NO in the Af-Art, Ef-Art and the macula densa may be important in the control of glomerular haemodynamics under various physiological and pathological conditions.     

Enhanced parenchymal arteriole tone and astrocyte signaling protect neurovascular coupling mediated parenchymal arteriole vasodilation in the spontaneously hypertensive rat

Functional hyperemia is the regional increase in cerebral blood flow upon increases in neuronal activity which ensures that the metabolic demands of the neurons are met. Hypertension is known to impair the hyperemic response; however, the neurovascular coupling mechanisms by which this cerebrovascular dysfunction occurs have yet to be fully elucidated. To determine whether altered cortical parenchymal arteriole function or astrocyte signaling contribute to blunted neurovascular coupling in hypertension, we measured parenchymal arteriole reactivity and vascular smooth muscle cell Ca²⁺ dynamics in cortical brain slices from normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. We found that vasoconstriction in response to the thromboxane A₂ receptor agonist U46619 and basal vascular smooth muscle cell Ca²⁺ oscillation frequency were significantly increased in parenchymal arterioles from SHR. In perfused and pressurized parenchymal arterioles, myogenic tone was significantly increased in SHR. Although K⁺-induced parenchymal arteriole dilations were similar in WKY and SHR, metabotropic glutamate receptor activation-induced parenchymal arteriole dilations were enhanced in SHR. Further, neuronal stimulation-evoked parenchymal arteriole dilations were similar in SHR and WKY. Our data indicate that neurovascular coupling is not impaired in SHR, at least at the level of the parenchymal arterioles.     

Retinal vascular calibre and response to light exposure and serial imaging

Purpose: To investigate whether retinal vessel calibre measurements on optical retinal photography are affected by light and dark exposure prior to photography and whether the vessel calibre changes during an imaging sequence of several images. Methods: Digital optical retinal photographs were obtained from 32 healthy adults in two separate image sequences of six images during 1 min; one sequence with 10 min of dark exposure and one with 10 min of light exposure prior to imaging. Retinal arteriolar and venular calibres were measured computer‐assisted and summarized as central retinal artery and vein equivalents (CRAE and CRVE). Outcome measures were difference in calibres after prior light versus prior dark exposure and difference in calibre during each of the two imaging sequences. Results: CRVE was wider with prior light exposure (2.7%, p = 0.0001), comparing the first image in each image sequence. Within each sequence, there was a venular dilatation from first to last image, both with prior light exposure (1.7%, p = 0.0003) and prior dark exposure (3.1%, p < 0.0001), with the change less pronounced with prior light exposure (p = 0.0164). CRAE showed no significant change in either outcome. Conclusions: Retinal venular calibre was wider with light exposure prior to imaging and increased slightly during the imaging sequences, less pronounced after prior light than dark exposure. Measurement error due to these effects will probably be reduced by avoiding dark prior to imaging, and a possible bias effect of endothelial dysfunction may possibly be reduced by measuring calibre on an image taken early in the image sequence.     

CELL-SPECIFIC PROTEIN AND GENE EXPRESSION IN THE JUXTAGLOMERULAR APPARATUS

1. The juxtaglomerular apparatus (JGA) consists of a tubular component, the macula densa (MD), attached to a vascular component consisting of the afferent and efferent arterioles and the extraglomerular mesangium. The JGA is richly innervated by sympathetic fibres. 2. The MD is morphologically, histochemically and functionally different from the ascending thick portion of the loop of Henle where it is located. 3. The vascular component includes the vascular smooth muscle cells of the arteriole, the renin-producing cells or juxtaglomerular cells, extraglomerular mesangial cells (Goormagh-tigh cells) and endothelial cells. They are coupled by gap junctions. 4. Physiological evidence indicates that the composition of tubular fluid at the MD regulates renin secretion and glomerular haemodynamics and that the JGA is important in the maintenance of body salt-water homeostasis. Evidence suggests that the MD exerts its action on the vascular component through a paracrine mechanism.     

Oxygen tension in rat cerebral cortex microvessels in acute anemia

Polarigraphic microelectrodes were used to study the distribution of oxygen tension (pO(2)) in arterioles (lumen diameters 8-80 microm) and venules (lumen diameters 8-120 microm) in the rat cerebral cortex during acute reductions in blood hemoglobin ([Hb]). Isovolumic hemodilution with 5% albumin solution was performed in steps from an initial [Hb] of 14.1 +/- 0.3 g/dl (control) to 9.8 +/- 0.3 g/dl (step 1), 6.6 +/- 0.4 g/dl (step 2), and 4.6 +/- 0.3 g/dl (step 3). Mild anemia (step 1, hematocrit 30%) led to an increase in pO(2) in the arterial side of the microcirculatory bed, with virtually no change in pO(2) in the venous side. Step 2 (hematocrit 20%) was accompanied by a further insignificant increase in pO(2) in arterioles, while there was a significant reduction (on average to 32 mmHg) in venules. Step 3 (hematocrit 13-14%) led to a (statistically insignificant) increase in pO(2) in arterioles. pO(2) in venules decreased, on average, to 27 mmHg; the proportion of smallest venules with low pO(2) values (less than 20 mmHg) increased to 31% (from 3% in controls). In some capillaries, pO(2) was 5-10 mmHg, which was an indicator of the presence of hypoxic zones in brain tissues. These zones primarily arose close to the smallest capillary and venous microvessels, with slowed or impaired blood flow.     

第483例——肾功能异常,间断右手麻木

患者女,65岁。因血肌酐升高(155μmol/L)2月余就诊。入院后肾脏穿刺活检组织病理提示,肾小血管闭塞及肾间质纤维化,起初考虑为全身动脉粥样硬化一部分,予瑞舒伐他汀20 mg每晚1次、福辛普利10 mg每日1次、倍他乐克47.5 mg每日1次、阿司匹林0.1 g每日1次治疗,血肌酐仍波动于200μmol/L左右。进一步完善肾组织病理刚果红染色,发现砖红色物质普遍沉积于肾小叶间动脉及入球小动脉管壁内,结合血游离轻链κ340 mg/L,血游离轻链κ/λ为10.932,肾轻链型淀粉样变诊断明确。予硼替佐米(2 mg,第1、8、15、22天皮下注射)、环磷酰胺(0.3 g,第1、8、15、22天口服)、地塞米松(40 mg,第1、8、15、22天口服)方案(BCD)化疗,每28天1个疗程,化疗3个疗程后,患者达到部分缓解,血肌酐降至180μmol/L。     

5-HT7 receptors mediate dilation of rat cremaster muscle arterioles in vivo

Objective

Serotonin (5-HT) infusion in vivo causes hypotension and a fall in total peripheral resistance. However, the vascular segment and the receptors that mediate this response remain in question. We hypothesized that 5-HT₇ receptors mediate arteriolar dilation to 5-HT in skeletal muscle microcirculation.

Methods

Cremaster muscles of isoflurane-anesthetized male Sprague-Dawley rats were prepared for in vivo microscopy of third- and fourth-order arterioles and superfused with physiological salt solution at 34°C. Quantitative real-time PCR (RT-PCR) was applied to pooled samples of first- to third-order cremaster arterioles (2–4 rats/sample) to evaluate 5-HT₇ receptor expression.

Results

Topical 5-HT (1–10 nmols) or the 5-HT_1/7 receptor agonist, 5-carboxamidotryptamine (10–30 nM), dilated third- and fourth-order arterioles, responses that were abolished by 1 μM SB269970, a selective 5-HT₇ receptor antagonist. In contrast, dilation induced by the muscarinic agonist, methacholine (100 nmols) was not inhibited by SB269970. Serotonin (10 nmols) failed to dilate cremaster arterioles in 5-HT₇ receptor knockout rats whereas arterioles in wild-type litter mates dilated to 1 nmol 5-HT, a response blocked by 1 μM SB269970. Quantitative RT-PCR revealed that cremaster arterioles expressed mRNA for 5-HT₇ receptors.

Conclusions

5-HT₇ receptors mediate dilation of small arterioles in skeletal muscle and likely contribute to 5-HT-induced hypotension, in vivo.