scholarly journals Blood Flow Sensing Mechanism via Calcium Signaling in Vascular Endothelium

2010 ◽  
Vol 130 (11) ◽  
pp. 1407-1411 ◽  
Author(s):  
Kimiko YAMAMOTO ◽  
Joji ANDO
Keyword(s):  
Blood Flow ◽  
Calcium Signaling ◽  
Vascular Endothelium ◽  
Sensing Mechanism ◽  
Flow Sensing

scholarly journals Adrenergic control of vascular resistance varies in muscles composed of different fiber types: influence of the vascular endothelium

2011 ◽  
Vol 301 (3) ◽  
pp. R783-R790 ◽  
Author(s):  
Bradley J. Behnke ◽  
Robert B. Armstrong ◽  
Michael D. Delp
Keyword(s):  
Blood Flow ◽  
Vascular Resistance ◽  
Vascular Endothelium ◽  
Fold Increase ◽  
Male Rats ◽  
Type I ◽  
Fiber Types ◽  
Fast Twitch Muscle ◽  
Dose Responses ◽  
Fast Twitch

The influence of the sympathetic nervous system (SNS) upon vascular resistance is more profound in muscles comprised predominately of low-oxidative type IIB vs. high-oxidative type I fiber types. However, within muscles containing high-oxidative type IIA and IIX fibers, the role of the SNS on vasomotor tone is not well established. The purpose of this study was to examine the influence of sympathetic neural vasoconstrictor tone in muscles composed of different fiber types. In adult male rats, blood flow to the red and white portions of the gastrocnemius (GastRed and GastWhite, respectively) and the soleus muscle was measured pre- and postdenervation. Resistance arterioles from these muscles were removed, and dose responses to α1-phenylephrine or α2-clonidine adrenoreceptor agonists were determined with and without the vascular endothelium. Denervation resulted in a 2.7-fold increase in blood flow to the soleus and GastRed and an 8.7-fold increase in flow to the GastWhite. In isolated arterioles, α2-mediated vasoconstriction was greatest in GastWhite (∼50%) and less in GastRed (∼31%) and soleus (∼17%); differences among arterioles were abolished with the removal of the endothelium. There was greater sensitivity to α1-mediated vasoconstriction in the GastWhite and GastRed vs. the soleus, which was independent of whether the endothelium was present. These data indicate that 1) control of vascular resistance by the SNS in high-oxidative, fast-twitch muscle is intermediate to that of low-oxidative, fast-twitch and high-oxidative, slow-twitch muscles; and 2) the ability of the SNS to control blood flow to low-oxidative type IIB muscle appears to be mediated through postsynaptic α1- and α2-adrenoreceptors on the vascular smooth muscle.

Association of systemic cardio-vasculature status with retinal vascular endothelium in diabetes

2020 ◽  
Vol 1 (1) ◽  
pp. 52-57
Author(s):  
Galina Dimitrova ◽  
Keyword(s):  
Blood Flow ◽  
Diabetic Retinopathy ◽  
Optic Nerve ◽  
Arterial Stiffness ◽  
Vascular Endothelium ◽  
Lamina Cribrosa ◽  
Central Retinal Artery ◽  
Diabetic Patients ◽  
Retinal Artery ◽  
Central Retinal Vein

The relationship between diabetic retinopathy and macro-vascular complications in diabetes suggests a pathogenic association between these conditions. Vascular endothelium has been identified as a main site of blood vessel injury in diabetes. Diabetic retinopathy is associated with systemic arterial stiffness and altered vascular endothelium function and structure. Retinal vasculature endothelium at the macula, arterio-venous crossings, and in the optic nerve at the lamina cribrosa region is reported to differ from the endothelium in the rest of the retinal blood vessels. The central retinal artery and vein are in close proximity in the optic nerve where they share a common adventitia; thus, increased arterial wall stiffness and thickness may affect blood flow in the neighboring central retinal vein in this region. Moreover, increased arterial stiffness in small arterial beds is associated with retinal venular widening; it suggests the possibility of central retinal artery compressing the central retinal vein at the lamina cribrosa, thereby compromising venular outflow in the retina of diabetic patients. Altered blood flow in the central retinal vein in the postlaminar region has been detected in patients who experience progression of diabetic retinopathy. Increased hydrostatic pressure in the central retinal vein may play a major role in the pathogenesis of diabetic retinopathy. The aim of this review article is to emphasize this pathogenetic mechanism that has often been overlooked.

Coronary vasodilation mediated by T cells expressing choline acetyltransferase

2021 ◽  
Vol 321 (5) ◽  
pp. H933-H939
Author(s):  
Adrian H. Chester ◽  
Ann McCormack ◽  
Edmund J. Miller ◽  
Mohamed N. Ahmed ◽  
Magdi H. Yacoub
Keyword(s):  
T Cells ◽  
Blood Flow ◽  
Blood Vessel ◽  
Coronary Blood Flow ◽  
Choline Acetyltransferase ◽  
Vascular Endothelium ◽  
Coronary Circulation ◽  
Direct Interaction ◽  
Coronary Vasodilation ◽  
Ischemic Events

This study shows ChAT-expressing T cells can induce vasodilation of the blood vessel in the coronary circulation and that this effect relies on a direct interaction between T cells and the coronary vascular endothelium. The study establishes a potential immunomodulatory role for T cells in the coronary circulation. The present findings offer an additional possibility that a deficiency of ChAT-expressing T cells could contribute to reduced coronary blood flow and ischemic events in the myocardium.

scholarly journals Mechanisms of Stroke in Sickle Cell Disease: Sickle Erythrocytes Decrease Cerebral Blood Flow in Rats After Nitric Oxide Synthase Inhibition

Blood ◽  
1997 ◽  
Vol 89 (12) ◽  
pp. 4591-4599 ◽  
Author(s):  
James A. French ◽  
Dermot Kenny ◽  
J. Paul Scott ◽  
Raymond G. Hoffmann ◽  
James D. Wood ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Vascular Endothelium ◽  
Cell Disease ◽  
Cerebral Microvessels ◽  
Doppler Flowmetry ◽  
Cranial Window

Abstract The etiology of stroke in sickle cell disease is unclear, but may involve abnormal red blood cell (RBC) adhesion to the vascular endothelium and altered vasomotor tone regulation. Therefore, we examined both the adhesion of sickle (SS)-RBCs to cerebral microvessels and the effect of SS-RBCs on cerebral blood flow when the nitric oxide (NO) pathway was inhibited. The effect of SS-RBCs was studied in the rat cerebral microcirculation using either a cranial window for direct visualization of infused RBCs or laser Doppler flowmetry (LDF ) to measure RBC flow. When fluorescently labeled human RBCs were infused into rats, SS-RBCs had increased adhesion to rat cerebral microvessels compared with control AA-RBCs (P = .01). Next, washed SS-RBCs or AA-RBCs were infused into rats prepared with LDF probes after pretreatment (40 mg/kg intravenously) with the NO synthase inhibitor, N-ω-nitro-L-arginine methyl ester (L-NAME), or the control isomer, D-NAME. In 9 rats treated with systemic L-NAME and SS-RBCs, 5 of 9 experienced a significant decrease in LDF and died within 30 minutes after the RBC infusion (P = .0012). In contrast, all control groups completed the experiment with stable LDF and hemodynamics. Four rats received a localized superfusion of L-NAME (1 mmol/L) through the cranial window followed by infusion of SS-RBCs. Total cessation of flow in all observed cerebral microvessels occurred in 3 of 4 rats within 15 minutes after infusion of SS-RBCs. We conclude that the NO pathway is critical in maintaining cerebral blood flow in the presence of SS-RBCs in this rat model. In addition, the enhanced adhesion of SS-RBCs to rat brain microvessels may contribute to cerebral vaso-occlusion either directly, by disrupting blood flow, or indirectly, by disturbing the vascular endothelium.

Effects of Pan-Selectin Antagonist GMI-1070 on the Treatment of Vaso-Occlusion in Sickle Cell Mice

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 535-535 ◽  
Author(s):  
Jungshan Chang ◽  
John T Patton ◽  
Paul S. Frenette ◽  
John L. Magnani
Keyword(s):  
Blood Flow ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Small Molecule ◽  
Vascular Endothelium ◽  
Intravital Microscopy ◽  
Blood Cells ◽  
Tnf Α ◽  
Sickle Red Blood Cells ◽  
Adherent Leukocytes

Abstract Acute vaso-occlusion (VOC) in patients with sickle cell disease (SCD) induces intense pain arising from organ damage and is the major cause of morbidity and mortality. Hypoxia and abnormal sickle red blood cells (RBC) induce inflammatory mediators and activation of the vascular endothelium leading to the recruitment of adherent leukocytes and sickle RBC followed by aggregates that eventually occlude blood flow. Previous studies have implicated the critical roles of cell adhesion molecules E- and P-selectins by using intravital microscopy in SCD mice (Berkeley strain) with altered genetic backgrounds (SCD transplanted in recipients lacking E-and P-selectins), or antibodies against endothelial selectins, or small molecules directed against the selectins. Here, we designed a treatment protocol for this SCD mouse model, in which a small molecule pan-selectin antagonist (GMI-1070) is administered to sickle cell mice late in the process of established vaso-occlusion in order to test the effects of GMI-1070 in a more clinically relevant model. GMI-1070 is a small molecule pan-selectin antagonist designed on the bioactive conformation of the carbohydrate ligand and inhibits leukocyte adhesion to activated endothelium in vitro with particularly strong activity against E-selectin (IC50 = 3.4 μM). Berkeley SCD mice were generated by bone marrow transplantation into lethally irradiated C57BL/6 male mice and the fully engrafted (100% donor RBC chimerism) mice were used for intravital microscopy experiments. VOC events were induced by injection with TNF-α at time 0 and the formation of occlusions were allowed to proceed as long as possible just prior to the death of the control mice. GMI-1070 (20 mg/kg) or vehicle (PBS pH 7.4) were administered at t = 110 min. Post-capillary and collecting venules in the cremaster muscle were analyzed for effects on an established VOC event. Under these conditions, GMI-1070 significantly increased the microcirculatory blood flow to levels observed in non-sickle cell mice (vehicle: 237 ± 15 nL/sec; GMI-1070: 533 ± 58 nL/sec; p<0.0001). The recruitment of adherent leukocytes to the vascular endothelium was also significantly reduced (vehicle: 2235 ± 156; GMI-1070: 1270 ± 203 cells/mm2; p=0.0013), and there were significant and dramatic reductions in the capture of sickle red blood cells to adherent leukocytes (vehicle: 0.68 ± 0.27; GMI-1070: 0.03 ± 0.01 interactions/WBC, min, 100ml; p=0.0003). Mice began to succumb to VOC within 2.5 hours after injection of TNF-α and surgical trauma which continued until all of the control SCD mice died. Administration of GMI-1070 prevented the death of half of the treated mice within the timeframe of the experiment and extended the median survival of mice from 5 hours (control, vehicle-treated) to greater than 9 hours for the GMI-1070- treated SCD mice (p = 0.0067). These studies show that GMI-1070 can significantly and dramatically improve the condition and survival of the animals with a severe VOC even when dosed well after the initiating challenge. Thus these data strongly support the use of GMI-1070 for the treatment of patients in acute vaso-occlusive crisis. GMI-1070 is currently in a Phase I clinical trial.

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