Low intravascular pressure activates endothelial cell TRPV4 channels,local Ca2+ events,and IKCa channels,reducing arteriolar tone

Endothelial cell (EC) Ca²⁺-activated K channels (SK_Ca and IK_Ca channels) generate hyperpolarization that passes to the adjacent smooth muscle cells causing vasodilation. IK_Ca channels focused within EC projections toward the smooth muscle cells are activated by spontaneous Ca²⁺ events (Ca²⁺ puffs/pulsars). We now show that transient receptor potential, vanilloid 4 channels (TRPV4 channels) also cluster within this microdomain and are selectively activated at low intravascular pressure. In arterioles pressurized to 80 mmHg, ECs generated low-frequency (∼2 min⁻¹) inositol 1,4,5-trisphosphate receptor-based Ca²⁺ events. Decreasing intraluminal pressure below 50 mmHg increased the frequency of EC Ca²⁺ events twofold to threefold, an effect blocked with the TRPV4 antagonist RN1734. These discrete events represent both TRPV4-sparklet- and nonsparklet-evoked Ca²⁺ increases, which on occasion led to intracellular Ca²⁺ waves. The concurrent vasodilation associated with increases in Ca²⁺ event frequency was inhibited, and basal myogenic tone was increased, by either RN1734 or TRAM-34 (IK_Ca channel blocker), but not by apamin (SK_Ca channel blocker). These data show that intraluminal pressure influences an endothelial microdomain inversely to alter Ca²⁺ event frequency; at low pressures the consequence is activation of EC IK_Ca channels and vasodilation, reducing the myogenic tone that underpins tissue blood-flow autoregulation.     

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.     

A Role for Dietary Copper in Nitric Oxide-Mediated Vasodilation

Objective : This study was designed to investigate the role of dietary copper in nitric oxide-mediated arteriolar dilation. Methods : Male weanling Sprague—Dawley rats were fed a purified diet that was either copper-adequate (6.0 μg Cu per g diet) or copper-deficient (0.3 μg Cu per g diet) for a period of 4 weeks. Each rat was anesthetized with pentobarbital and its cremaster muscle was positioned in a Krebs'-fdled bath to which graded concentrations of vasoactive agents were added. In the first series, responses to norepineph-rine (NE 10^?9-10^?6 M) and acetylcholine (ACH 10^?7-10^?4 M) were compared in third-order arterioles. Second, the dilator response to 10^?5 M ACH in the absence and presence of 240 U/ml Cu, Zn-superoxide dismutase (SOD) was determined. Third, arteriolar dilation was determined in response to NO-independent stimulation of soluble guanylate cyclase with hydrogen peroxide (10^?7-10^?5 M) and to dibutyryl cGMP (10^?6-10^?4 M), dibutyryl cAMP (10^?6-10^?4 M), and papaverine (10^?4M). Results : The arteriole constrictor response to NE and the dilator response to hydrogen peroxide, dibutyryl cGMP and cAMP, and papaverine were not different between the dietary groups. Copper deficiency attenuated the ACH-induced dilation, but the response was restored in the presence of SOD. Conclusions : The inactivation of cytosolic Cu, Zn-SOD by restriction of dietary copper results in the depression of NO-mediated vascular smooth-muscle relaxation probably by interaction of NO with superoxide.     

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.     

Studies in long-pulsed potassium tritanyl phosphate laser for the treatment of spider naevi and perialar telangiectasia

Utilization of a 1-10 msec vascular laser to treat facial vessels to limit purpura has become available in recent years. Its efficacy and morbidity in the treatment of common vascular lesions require exploration. We have assessed the relative outcomes and morbidity from a single treatment session of two patterns of 'difficult to treat' facial telangiectasia - perialar vessels and spider naevi - with such a system. Two prospective clinical studies with long pulse 532 nm potassium tritanyl phosphate (KTP) laser were performed with subjective and independent objective assessment at 3 days, 1 week and 4 weeks in both studies. Perialar vessels showed good to excellent improvement subjectively at 4 weeks in 53% (8/15), spider naevi in 83% (20/24). Pain of treatment was substantially greater treating perialar telangiectasia than when treating spider naevi (P < 0.01). Morbidity was low in both groups with no long-term complications. Despite the clinical end-point of vessel disappearance at time of treatment and good early improvement in the appearance of perialar vessels, the failure rate was significant at 1 month follow up. It would appear that spider naevi behave more predictably, with vessel disappearance at time of treatment most often forecasting a successful outcome. Although not statistically significant, spider naevi probably respond better than perialar vessels to a single treatment with this laser.     

Methods for isolation and characterization of intracerebral arterioles in the C57/BL6 wild-type mouse

Vascular control mechanisms have been studied extensively in mice. However, an in vitro characterization of penetrating intracerebral arterioles has not been reported. We describe methods for isolation and cannulation for mouse intracerebral arterioles. This technique allows analysis of mouse cerebral arteriolar physiology and pharmacology without the confounding influences of the surrounding brain elements. Penetrating intracerebral arterioles from adult C57/BL6 wild-type (WT) mice were isolated at 4 °C, transferred to an inverted microscope and cannulated at both ends using a dual glass micropipette system, wherein intraluminal flow (0.2 μl/min) and pressure (60 mmHg) were maintained. The arterioles developed spontaneous tone when the chamber was warmed to 37 °C, with the resulting diameter reaching 68.4±0.9% of passive diameter (29.8±1.1 μm). After the development of spontaneous tone, incremental changes in luminal pressure from 20 to 140 mmHg induced myogenic responses. Acidosis (pH 6.8) and alkalosis (pH 7.6) caused dilation (20.0±1.4%) and constriction (17.2±1.4%), respectively. Extraluminal adenosine (ADO (10 μM); 24.3±3.6%) and sodium nitroprusside (SNP (10 μM); 28.6±4.1%) and intraluminal adenosine 5′-triphosphate (ATP (10 μM); 20.0±3.9%) resulted in vasodilation similar in magnitude to that observed in rat arterioles. This information provides a foundation for elucidating cerebral vascular control mechanisms in genetically engineered mice.     

In vivo properties of potassium channels in cerebral blood vessels during diabetes mellitus

OBJECTIVE: While potassium (K+) channels are important in basal tone and dilatation of large and small cerebral vessels, the effect of diabetes mellitus on K+ channels remains unclear. The goal of this study was to identify the influence of diabetes on responses of cerebral vessels to inhibition/activation of K+ channels. METHODS: The authors measured in vivo responses of pial arterioles and the basilar artery to inhibition/activation of K+ channels in nondiabetic and diabetic rats using intravital microscopy. RESULTS: Pial arterioles from nondiabetic and diabetic rats constricted to barium chloride (BaCl2) and 4-aminopyridine (4-AP). However, the magnitude of vasoconstriction to BaCl2 was greater in nondiabetic than in diabetic rats. Tetraethylammonium (TEA) did not alter diameter of pial arterioles in nondiabetic or diabetic rats. In addition, dilatation of pial arterioles to KCl and NS-1619 was less in diabetic compared to nondiabetic rats. The basilar artery from nondiabetic and diabetic rats constricted in a similar manner to BaCl2 and 4-AP. In contrast, vasoconstriction to TEA was greater in diabetic than nondiabetic rats. Similar to that reported for pial arterioles, dilatation of the basilar artery to KCl and NS-1619 was less in diabetic than nondiabetic rats. CONCLUSIONS: Inward-rectifier (Kir) and voltage-dependent (Kv), but not calcium-activated (Kca), K+ channels are active under basal conditions in pial arterioles, while Kir, Kv, and Kca are active under basal conditions in the basilar artery of nondiabetic and diabetic rats. In addition, activation of Kir and Kca channels produces less cerebral vasodilatation in diabetic compared to nondiabetic rats. These findings provide new and important information regarding the influence of diabetes on the role of K+ channels in the regulation of cerebral vascular diameter.     

Nitroglycerin enhances cGMP expression in specific neuronal and cerebrovascular structures of the rat brain

Although the involvement of nitric oxide (NO) in mediating pain and neurovascular coupling is well established, the precise mechanisms sustaining these effects are still unclear. Cyclic GMP (cGMP) probably represents the main effector of the biological effects of NO at the vascular and neuronal levels. Nitroglycerin is a NO donor, which easily crosses the blood brain barrier. Several reports have suggested that the study of nitroglycerin effects upon neuronal and cerebrovascular elements is a useful animal model for investigating the pathophysiological mechanisms underlying migraine. In this study, the anatomic distribution of cGMP in the rat brain was evaluated at serial time-points after systemic administration of nitroglycerin or vehicle. The results show an increase in cGMP immunoreactivity in the nucleus trigeminalis caudalis and in the superficial cortical arterioles 2, 3 and 4h after the drug administration. The data obtained sustains the idea that cGMP is an important mediator of nitroglycerin effect in vascular and neuronal structures that are critical elements for the transmission of cephalic pain.     

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。     

活血化痰通络方早期治疗风痰瘀阻证急性小动脉闭塞型脑梗死的临床研究

目的 观察活血化痰通络方早期治疗风痰瘀阻证急性小动脉闭塞型脑梗死的临床疗效.方法 将2018年8月1日—2019年9月30日在湖北省中西医结合医院神经内科住院的240例风痰瘀阻证急性小动脉闭塞型脑梗死患者随机分成治疗组和对照组,每组120例.对照组给予常规西药治疗,治疗组在西药治疗基础上给予活血化痰通络方治疗2周.观察...