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Annual Review of Physiology Feb 2022The vast majority of the brain's vascular length is composed of capillaries, where our understanding of blood flow control remains incomplete. This review synthesizes... (Review)
Review
The vast majority of the brain's vascular length is composed of capillaries, where our understanding of blood flow control remains incomplete. This review synthesizes current knowledge on the control of blood flow across microvascular zones by addressing issues with nomenclature and drawing on new developments from in vivo optical imaging and single-cell transcriptomics. Recent studies have highlighted important distinctions in mural cell morphology, gene expression, and contractile dynamics, which can explain observed differences in response to vasoactive mediators between arteriole, transitional, and capillary zones. Smooth muscle cells of arterioles and ensheathing pericytes of the arteriole-capillary transitional zone control large-scale, rapid changes in blood flow. In contrast, capillary pericytes downstream of the transitional zone act on slower and smaller scales and are involved in establishing resting capillary tone and flow heterogeneity. Many unresolved issues remain, including the vasoactive mediators that activate the different pericyte types in vivo, the role of pericyte-endothelial communication in conducting signals from capillaries to arterioles, and how neurological disease affects these mechanisms.
Topics: Arterioles; Capillaries; Central Nervous System; Cerebrovascular Circulation; Humans; Pericytes
PubMed: 34672718
DOI: 10.1146/annurev-physiol-061121-040127 -
Neuropathology and Applied Neurobiology Feb 2023Cerebral microvascular disease (MVD) is an important cause of vascular cognitive impairment. MVD is heterogeneous in aetiology, ranging from universal ageing to the... (Review)
Review
Cerebral microvascular disease (MVD) is an important cause of vascular cognitive impairment. MVD is heterogeneous in aetiology, ranging from universal ageing to the sporadic (hypertension, sporadic cerebral amyloid angiopathy [CAA] and chronic kidney disease) and the genetic (e.g., familial CAA, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL] and cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy [CARASIL]). The brain parenchymal consequences of MVD predominantly consist of lacunar infarcts (lacunes), microinfarcts, white matter disease of ageing and microhaemorrhages. MVD is characterised by substantial arteriolar neuropathology involving ubiquitous vascular smooth muscle cell (SMC) abnormalities. Cerebral MVD is characterised by a wide variety of arteriolar injuries but only a limited number of parenchymal manifestations. We reason that the cerebral arteriole plays a dominant role in the pathogenesis of each type of MVD. Perturbations in signalling and function (i.e., changes in proliferation, apoptosis, phenotypic switch and migration of SMC) are prominent in the pathogenesis of cerebral MVD, making 'cerebral angiomyopathy' an appropriate term to describe the spectrum of pathologic abnormalities. The evidence suggests that the cerebral arteriole acts as both source and mediator of parenchymal injury in MVD.
Topics: Humans; Arterioles; Cerebral Infarction; CADASIL; Brain; Cerebral Amyloid Angiopathy; Neuromuscular Diseases
PubMed: 36564356
DOI: 10.1111/nan.12875 -
The Journal of Neuroscience : the... Aug 2017Astrocytes can control basal synaptic strength and arteriole tone via their resting Ca activity. However, whether resting astrocyte Ca can adjust to a new steady-state...
Astrocytes can control basal synaptic strength and arteriole tone via their resting Ca activity. However, whether resting astrocyte Ca can adjust to a new steady-state level, with an impact on surrounding brain cells, remains unknown. Using two-photon Ca imaging in male rat acute brain slices of the somatosensory neocortex, we found that theta burst neural activity produced an unexpected long-lasting reduction in astrocyte free Ca in the soma and endfeet. The drop in intracellular Ca was attenuated by antagonists targeting multiple ionotropic and metabotropic glutamate receptors, and intracellular cascades involved Ca stores and nitric oxide. The reduction in astrocyte endfoot Ca was coincident with an increase in arteriole tone, and both the Ca drop and the tone change were prevented by an NMDA receptor antagonist. Astrocyte patch-clamp experiments verified that the glutamate receptors in question were located on astrocytes and that Ca changes within astrocytes were responsible for the long-lasting change in arteriole diameter caused by theta burst neural activity. In astrocytes from animals that lived in an enriched environment, we measured a relatively lower resting Ca level that occluded any further drop in Ca in response to theta burst activity. These data suggest that electrically evoked patterns of neural activity or natural experience can adjust steady-state resting astrocyte Ca and that the effect has an impact on basal arteriole diameter. The field of astrocyte-neuron and astrocyte-arteriole interactions is currently in a state of refinement. Experimental evidence suggests that direct manipulation of astrocyte-free Ca regulates synaptic signaling and local blood flow control; however, experiments fail to link synaptically evoked astrocyte Ca transients and immediate changes to various astrocyte-mediated processes. To clarify this discrepancy, we examined a different aspect of astrocyte Ca: the resting, steady-state free Ca of astrocytes, its modulation, and its potential role in the tonic regulation of surrounding brain cells. We found that or neural activity induced a long-lasting reduction in resting free astrocyte Ca and that this phenomenon changed arteriole tone.
Topics: Animals; Arterioles; Astrocytes; Calcium; Calcium Signaling; Male; Mice; Mice, Transgenic; Organ Culture Techniques; Rats; Rats, Sprague-Dawley; Somatosensory Cortex; Vasoconstriction
PubMed: 28733356
DOI: 10.1523/JNEUROSCI.0239-17.2017 -
Current Topics in Membranes 2022Ischemic heart disease is the leading cause of death and a major public health and economic burden worldwide with expectations of predicted growth in the foreseeable... (Review)
Review
Ischemic heart disease is the leading cause of death and a major public health and economic burden worldwide with expectations of predicted growth in the foreseeable future. It is now recognized clinically that flow-limiting stenosis of the large coronary conduit arteries as well as microvascular dysfunction in the absence of severe stenosis can each contribute to the etiology of ischemic heart disease. The primary site of coronary vascular resistance, and control of subsequent coronary blood flow, is found in the coronary microvasculature, where small changes in radius can have profound impacts on myocardial perfusion. Basal active tone and responses to vasodilators and vasoconstrictors are paramount in the regulation of coronary blood flow and adaptations in signaling associated with ion channels are a major factor in determining alterations in vascular resistance and thereby myocardial blood flow. K channels are of particular importance as contributors to all aspects of the regulation of arteriole resistance and control of perfusion into the myocardium because these channels dictate membrane potential, the resultant activity of voltage-gated calcium channels, and thereby, the contractile state of smooth muscle. Evidence also suggests that K channels play a significant role in adaptations with cardiovascular disease states. In this review, we highlight our research examining the role of K channels in ischemic heart disease and adaptations with exercise training as treatment, as well as how our findings have contributed to this area of study.
Topics: Humans; Constriction, Pathologic; Arterioles; Vascular Resistance; Hemodynamics; Myocardial Ischemia
PubMed: 36368873
DOI: 10.1016/bs.ctm.2022.09.004 -
Arteriosclerosis, Thrombosis, and... Sep 2020Quantitative relationships between the extent of injury and thrombus formation in vivo are not well understood. Moreover, it has not been investigated how increased...
OBJECTIVE
Quantitative relationships between the extent of injury and thrombus formation in vivo are not well understood. Moreover, it has not been investigated how increased injury severity translates to blood-flow modulation. Here, we investigated interconnections between injury length, clot growth, and blood flow in a mouse model of laser-induced thrombosis. Approach and Results: Using intravital microscopy, we analyzed 59 clotting events collected from the cremaster arteriole of 14 adult mice. We regarded injury length as a measure of injury severity. The injury caused transient constriction upstream and downstream of the injury site resulting in a 50% reduction in arteriole diameter. The amount of platelet accumulation and fibrin formation did not depend on arteriole diameter or deformation but displayed an exponentially increasing dependence on injury length. The height of the platelet clot depended linearly on injury length and the arteriole diameter. Upstream arteriolar constriction correlated with delayed upstream velocity increase, which, in turn, determined downstream velocity. Before clot formation, flow velocity positively correlated with the arteriole diameter. After the onset of thrombus growth, flow velocity at the injury site negatively correlated with the arteriole diameter and with the size of the above-clot lumen.
CONCLUSIONS
Injury severity increased platelet accumulation and fibrin formation in a persistently steep fashion and, together with arteriole diameter, defined clot height. Arterial constriction and clot formation were characterized by a dynamic change in the blood flow, associated with increased flow velocity.
Topics: Abdominal Muscles; Animals; Arterioles; Blood Coagulation; Blood Flow Velocity; Blood Platelets; Constriction, Pathologic; Disease Models, Animal; Fibrin; Intravital Microscopy; Male; Mice; Microscopy, Fluorescence; Severity of Illness Index; Thrombosis; Time Factors; Vascular System Injuries
PubMed: 32640902
DOI: 10.1161/ATVBAHA.120.314786 -
ELife Sep 2022Modulation of brain arteriole diameter is critical for maintaining cerebral blood pressure and controlling regional hyperemia during neural activity. However, studies of...
Modulation of brain arteriole diameter is critical for maintaining cerebral blood pressure and controlling regional hyperemia during neural activity. However, studies of hemodynamic function in health and disease have lacked a method to control arteriole diameter independently with high spatiotemporal resolution. Here, we describe an all-optical approach to manipulate and monitor brain arteriole contractility in mice in three dimensions using combined in vivo two-photon optogenetics and imaging. The expression of the red-shifted excitatory opsin, ReaChR, in vascular smooth muscle cells enabled rapid and repeated vasoconstriction controlled by brief light pulses. Two-photon activation of ReaChR using a spatial light modulator produced highly localized constrictions when targeted to individual arterioles within the neocortex. We demonstrate the utility of this method for examining arteriole contractile dynamics and creating transient focal blood flow reductions. Additionally, we show that optogenetic constriction can be used to reshape vasodilatory responses to sensory stimulation, providing a valuable tool to dissociate blood flow changes from neural activity.
Topics: Animals; Arterioles; Hemodynamics; Mice; Neocortex; Opsins; Optogenetics
PubMed: 36107146
DOI: 10.7554/eLife.72802 -
Microcirculation (New York, N.Y. : 1994) Jan 2018VSMCs in resistance arteries and arterioles express a diverse array of K channels with members of the K 1, K 2 and K 7 families being particularly important. Members of... (Review)
Review
VSMCs in resistance arteries and arterioles express a diverse array of K channels with members of the K 1, K 2 and K 7 families being particularly important. Members of the K channel family: (i) are highly expressed in VSMCs; (ii) are active at the resting membrane potential of VSMCs in vivo (-45 to -30 mV); (iii) contribute to the negative feedback regulation of VSMC membrane potential and myogenic tone; (iv) are activated by cAMP-related vasodilators, hydrogen sulfide and hydrogen peroxide; (v) are inhibited by increases in intracellular Ca and vasoconstrictors that signal through G -coupled receptors; (vi) are involved in the proliferative phenotype of VSMCs; and (vii) are modulated by diseases such as hypertension, obesity, the metabolic syndrome and diabetes. Thus, K channels participate in every aspect of the regulation of VSMC function in both health and disease.
Topics: Animals; Arterioles; Humans; Muscle, Smooth, Vascular; Potassium Channels, Voltage-Gated; Vasoconstriction; Vasodilation
PubMed: 28985443
DOI: 10.1111/micc.12421 -
Journal of the American Society of... Dec 2011The kidney is a highly vascularized organ that normally receives a fifth of the cardiac output. The unique spatial arrangement of the kidney vasculature with each... (Review)
Review
The kidney is a highly vascularized organ that normally receives a fifth of the cardiac output. The unique spatial arrangement of the kidney vasculature with each nephron is crucial for the regulation of renal blood flow, GFR, urine concentration, and other specialized kidney functions. Thus, the proper and timely assembly of kidney vessels with their respective nephrons is a crucial morphogenetic event leading to the formation of a functioning kidney necessary for independent extrauterine life. Mechanisms that govern the development of the kidney vasculature are poorly understood. In this review, we discuss the anatomical development, embryological origin, lineage relationships, and key regulators of the kidney arterioles and postglomerular circulation. Because renal disease is associated with deterioration of the kidney microvasculature and/or the reenactment of embryonic pathways, understanding the morphogenetic events and processes that maintain the renal vasculature may open new avenues for the preservation of renal structure and function and prevent the progression of renal disease.
Topics: Animals; Arterioles; Humans; Kidney; Neovascularization, Physiologic
PubMed: 22052047
DOI: 10.1681/ASN.2011080818 -
Basic & Clinical Pharmacology &... Jan 2012Arterioles are the blood vessels in the arterial side of the vascular tree that are located proximal to the capillaries and, in conjunction with the terminal arteries,... (Review)
Review
Arterioles are the blood vessels in the arterial side of the vascular tree that are located proximal to the capillaries and, in conjunction with the terminal arteries, provide the majority of resistance to blood flow. Consequently, arterioles are important contributors to the regulation of mean arterial pressure and tissue perfusion. Their wall consists of cellular and extracellular components that have been traditionally classified as conforming three layers: an intima containing endothelial cells sited on a basement membrane; a media made of an internal elastic lamina apposed by one or two layers of smooth muscle; and an adventitia composed mostly of collagen bundles, nerve endings and some fibroblasts. These components of the arteriolar wall are dynamically interconnected, providing a level of plasticity to the arteriolar wall that blurs the traditional boundaries of a rigid layered classification. This MiniReview focuses on the structural conformation of the arteriolar wall and shows how wall components interact spatially, functionally and temporally to control vascular diameter, regulate blood flow and maintain vascular permeability.
Topics: Animals; Arterioles; Capillary Permeability; Connective Tissue; Connective Tissue Cells; Humans; Tunica Intima; Tunica Media; Vascular Resistance
PubMed: 21989114
DOI: 10.1111/j.1742-7843.2011.00813.x -
Sao Paulo Medical Journal = Revista... 2018Investigation of alterations to retinal microvasculature may contribute towards understanding the role of such changes in the pathophysiology of several chronic...
BACKGROUND
Investigation of alterations to retinal microvasculature may contribute towards understanding the role of such changes in the pathophysiology of several chronic non-communicable diseases. The objective here was to evaluate the validity and reproducibility of retinal arteriole and venule diameter measurements made by Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) graders.
DESIGN AND SETTING
Cross-sectional study at six teaching and research institutions.
METHODS
To evaluate validity, each of 25 retinal images from the University of Wisconsin (gold standard) was measured by five ELSA-Brasil graders. To evaluate reproducibility, 105 images across the spectrum of vessel diameters were selected from 12,257 retinal images that had been obtained between 2010 and 2012, and each image was reexamined by the same grader and by an independent grader. All measurements were made using the Interactive Vessel Analysis (IVAN) software. Bland-Altman plots, paired t tests and intraclass correlation coefficients (ICCs) were analyzed.
RESULTS
Mean differences between ELSA-Brasil and gold-standard readings were 0.16 µm (95% CI -0.17-0.50; P = 0.31) for central retinal artery equivalent (CRAE), -0.21 µm (95% CI -0.56-0.14; P = 0.22) for central retinal vein equivalent (CRVE) and 0.0005 (95% CI -0.008-0.009; P = 0.55) for arteriole/venule ratio (AVR). Intragrader ICCs were 0.77 (95% CI 0.67-0.86) for CRAE, 0.90 (95% CI 0.780.96) for CRVE and 0.70 (0.55-0.83) for AVR. Intergrader ICCs were 0.75 (95% CI 0.64-0.85) for CRAE, 0.90 (95% CI 0.79-0.96) for CRVE and 0.68 (95% CI 0.55-0.82) for AVR.
CONCLUSIONS
Retinal microvascular diameter measurements are valid and present moderate to high intra and intergrader reproducibility in ELSA-Brasil.
Topics: Adult; Aged; Arterioles; Cross-Sectional Studies; Female; Humans; Image Interpretation, Computer-Assisted; Longitudinal Studies; Male; Middle Aged; Reproducibility of Results; Retinal Vessels; Socioeconomic Factors; Venules
PubMed: 30304202
DOI: 10.1590/1516-3180.2018.0227230718