Functional neuroimaging, such as fMRI, is based on coupling neuronal activity and accompanying changes in cerebral blood flow (CBF) and metabolism. However, the relationship between CBF and events at ...the level of the penetrating arterioles and capillaries is not well established. Recent findings suggest an active role of capillaries in CBF control, and pericytes on capillaries may be major regulators of CBF and initiators of functional imaging signals. Here, using two-photon microscopy of brains in living mice, we demonstrate that stimulation-evoked increases in synaptic activity in the mouse somatosensory cortex evokes capillary dilation starting mostly at the first- or second-order capillary, propagating upstream and downstream at 5–20 μm/s. Therefore, our data support an active role of pericytes in cerebrovascular control. The gliotransmitter ATP applied to first- and second-order capillaries by micropipette puffing induced dilation, followed by constriction, which also propagated at 5–20 μm/s. ATP-induced capillary constriction was blocked by purinergic P2 receptors. Thus, conducted vascular responses in capillaries may be a previously unidentified modulator of cerebrovascular function and functional neuroimaging signals.
Active nerve cells release vasodilators that increase their energy supply by dilating local blood vessels, a mechanism termed neurovascular coupling and the basis of BOLD functional neuroimaging ...signals. Here, we reveal a mechanism for cerebral blood flow control, a precapillary sphincter at the transition between the penetrating arteriole and first order capillary, linking blood flow in capillaries to the arteriolar inflow. The sphincters are encircled by contractile mural cells, which are capable of bidirectional control of the length and width of the enclosed vessel segment. The hemodynamic consequence is that precapillary sphincters can generate the largest changes in the cerebrovascular flow resistance of all brain vessel segments, thereby controlling capillary flow while protecting the downstream capillary bed and brain tissue from adverse pressure fluctuations. Cortical spreading depolarization constricts sphincters and causes vascular trapping of blood cells. Thus, precapillary sphincters are bottlenecks for brain capillary blood flow.
Recent evidence suggests that capillary pericytes are contractile and play a crucial role in the regulation of microcirculation. However, failure to detect components of the contractile apparatus in ...capillary pericytes, most notably α-smooth muscle actin (α-SMA), has questioned these findings. Using strategies that allow rapid filamentous-actin (F-actin) fixation (i.e. snap freeze fixation with methanol at -20°C) or prevent F-actin depolymerization (i.e. with F-actin stabilizing agents), we demonstrate that pericytes on mouse retinal capillaries, including those in intermediate and deeper plexus, express α-SMA. Junctional pericytes were more frequently α-SMA-positive relative to pericytes on linear capillary segments. Intravitreal administration of short interfering RNA (α-SMA-siRNA) suppressed α-SMA expression preferentially in high order branch capillary pericytes, confirming the existence of a smaller pool of α-SMA in distal capillary pericytes that is quickly lost by depolymerization. We conclude that capillary pericytes do express α-SMA, which rapidly depolymerizes during tissue fixation thus evading detection by immunolabeling.
Efficient insulin secretion requires a well-functioning pancreatic islet microvasculature. The dense network of islet capillaries includes the islet pericyte, a cell that has barely been studied. ...Here we show that islet pericytes help control local blood flow by adjusting islet capillary diameter. Islet pericytes cover 40% of the microvasculature, are contractile, and are innervated by sympathetic axons. Sympathetic adrenergic input increases pericyte activity and reduces capillary diameter and local blood flow. By contrast, activating beta cells by increasing glucose concentration inhibits pericytes, dilates islet capillaries, and increases local blood flow. These effects on pericytes are mediated by endogenous adenosine, which is likely derived from ATP co-released with insulin. Pericyte coverage of islet capillaries drops drastically in type 2 diabetes, suggesting that, under diabetic conditions, islets lose this mechanism to control their own blood supply. This may lead to inadequate insulin release into the circulation, further deteriorating glycemic control.
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•Contractile pericytes covering capillaries regulate pancreatic islet blood flow•Beta cell-derived adenosine relaxes pericytes and dilates islet capillaries•Sympathetic input activates islet pericytes to locally constrict capillaries•Pericyte coverage of islet capillaries drops during type 2 diabetes progression
Almaça et al. study pericyte cells, which wrap around capillary endothelial cells, in the islets of the pancreas and show that islet pericytes help control local blood flow by adjusting islet capillary diameter. They further show that this mechanism in lost in diabetes, which may lead to inadequate insulin supply.
Purpose
To investigate the OCTA parameters of the peripapillary retina and optic disk in Caucasian people of an older age group
Methods
Thirty‐four patients (68 eyes), 14 male and 20 female, mean age ...57.1 ± 9.6 were examine. All patients underwent OCT and OCTA examination (RTVue‐XR, Optovue), by using protocol ‘HD Angio Disk’ 4.5*4.5 mm. OCT and OCTA were used to measure the radial peripapillary capillaries (RPC, %) and retinal nerve fiber layer thickness (RNFL, µm), rim area, disc area, cup volume.
Results
Mean value of the RNFL thickness was 109.7 ± 11.1 µm. The lower value of the RNFL thickness was observed in ‘Tempo Inferior’ and ‘Tempo Superior’ segments. Rim area was 1.66 ± 0.33 mm2, disc area—1.87 ± 0.28 mm2. The mean value of RPC density in peripapillary retina was 52.2 ± 2.3%. The lower value of the RPC density was in ‘Nasal Inferior’ and ‘Superior Nasal’ segments, 48.9 ± 3.2% and 49.9 ± 3.1%, respectively.
This Article contains an error in Fig. 1, in which the structures of '(+)-Ac-L-Ta' and 'CTp' are drawn incorrectly. The correct version of Fig. 1 is shown below. The error has not been fixed in the ...original PDF and HTML versions of the Article.
BackgroundObjectives:We evaluated nailfold capillaroscopy (NFC) of interstitial pneumonia with autoimmune features (IPAF) and compared it with that of patients with CTD-ILD and idiopathic ...interstitial pneumonia (IIP).MethodsPatients with newly diagnosed as ILD were evaluated using NFC. Baseline demographic, clinical, serological, and high-resolution CT findings were collected. NFC was semi-quantitatively scored with six domains ranging from 0 to 18. In addition, the overall patterns (scleroderma/non-scleroderma patterns) were determined.ResultsA total of 81 patients (31 with CTD-ILD, 18 with IPAF, and 32 with IIP) were included. The non-specific interstitial pneumonia pattern was the most common ILD pattern in the CTD-ILD and IPAF groups, whereas the usual interstitial pneumonia pattern was the most common in the IIP group. The semi-quantitative score of the CTD-ILD group was higher than that of the IPAF or IIP groups (5.8 vs 4.2 vs 3.0, p < 0.001, respectively). Giant capillaries and haemorrhages were more frequently present in the CTD-ILD and IPAF groups than in the IIP group. A scleroderma pattern was present in 27.8% of the IPAF group, whereas none of the IIP patients showed a scleroderma pattern.ConclusionNFC findings may be useful in classifying patients with ILD into CTD-ILD/IPAF/IIP.Reference1Fischer A, Antoniou KM, Brown KK, et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J 2015;46:976-987.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
In the mammalian lung, an apparently homogenous mesh of capillary vessels surrounds each alveolus, forming the vast respiratory surface across which oxygen transfers to the blood
. Here we use ...single-cell analysis to elucidate the cell types, development, renewal and evolution of the alveolar capillary endothelium. We show that alveolar capillaries are mosaics; similar to the epithelium that lines the alveolus, the alveolar endothelium is made up of two intermingled cell types, with complex 'Swiss-cheese'-like morphologies and distinct functions. The first cell type, which we term the 'aerocyte', is specialized for gas exchange and the trafficking of leukocytes, and is unique to the lung. The other cell type, termed gCap ('general' capillary), is specialized to regulate vasomotor tone, and functions as a stem/progenitor cell in capillary homeostasis and repair. The two cell types develop from bipotent progenitors, mature gradually and are affected differently in disease and during ageing. This cell-type specialization is conserved between mouse and human lungs but is not found in alligator or turtle lungs, suggesting it arose during the evolution of the mammalian lung. The discovery of cell type specialization in alveolar capillaries transforms our understanding of the structure, function, regulation and maintenance of the air-blood barrier and gas exchange in health, disease and evolution.
Blood vessels in the central nervous system (CNS) are controlled by neuronal activity. For example, widespread vessel constriction (vessel tone) is induced by brainstem neurons that release the ...monoamines serotonin and noradrenaline, and local vessel dilation is induced by glutamatergic neuron activity. Here we examined how vessel tone adapts to the loss of neuron-derived monoamines after spinal cord injury (SCI) in rats. We find that, months after the imposition of SCI, the spinal cord below the site of injury is in a chronic state of hypoxia owing to paradoxical excess activity of monoamine receptors (5-HT
) on pericytes, despite the absence of monoamines. This monoamine-receptor activity causes pericytes to locally constrict capillaries, which reduces blood flow to ischemic levels. Receptor activation in the absence of monoamines results from the production of trace amines (such as tryptamine) by pericytes that ectopically express the enzyme aromatic L-amino acid decarboxylase (AADC), which synthesizes trace amines directly from dietary amino acids (such as tryptophan). Inhibition of monoamine receptors or of AADC, or even an increase in inhaled oxygen, produces substantial relief from hypoxia and improves motoneuron and locomotor function after SCI.
The transport of oxygen between blood and tissue is limited by blood's capillary transit time, understood as the time available for diffusion exchange before blood returns to the heart. If all ...capillaries contribute equally to tissue oxygenation at all times, this physical limitation would render vasodilation and increased blood flow insufficient means to meet increased metabolic demands in the heart, muscle, and other organs. In 1920, Danish physiologist August Krogh was awarded the Nobel Prize in Physiology or Medicine for his mathematical and quantitative, experimental demonstration of a solution to this conceptual problem: capillary recruitment, the active opening of previously closed capillaries to meet metabolic demands. Today, capillary recruitment is still mentioned in textbooks. When we suspect symptoms might represent hypoxia of a vascular origin, however, we search for relevant, flow-limiting conditions in our patients and rarely ascribe hypoxia or hypoxemia to short capillary transit times. This review describes how natural changes in capillary transit-time heterogeneity (CTH) and capillary hematocrit (HCT) across open capillaries during blood flow increases can account for a match of oxygen availability to metabolic demands in normal tissue. CTH and HCT depend on a number of factors: on blood properties, including plasma viscosity, the number, size, and deformability of blood cells, and blood cell interactions with capillary endothelium; on anatomical factors including glycocalyx, endothelial cells, basement membrane, and pericytes that affect the capillary diameter; and on any external compression. The review describes how risk factor- and disease-related changes in CTH and HCT interfere with flow-metabolism coupling and tissue oxygenation and discusses whether such
contributes to vascular disease pathology.
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