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The Journal of Physiology Mar 2023The brain is an energy hog, consuming available energy supplies at a rate out of all proportion to its relatively small size. This outsized demand, largely reflecting... (Review)
Review
The brain is an energy hog, consuming available energy supplies at a rate out of all proportion to its relatively small size. This outsized demand, largely reflecting the unique computational activity of the brain, is met by an ensemble of neurovascular coupling mechanisms that link neuronal activity with local increases in blood delivery. This just-in-time replenishment strategy, made necessary by the limited energy-storage capacity of neurons, complicates the nutrient-delivery task of the cerebral vasculature, layering on a temporo-spatial requirement that invites - and challenges - mechanistic interpretation. The centre of gravity of research efforts to disentangle these mechanisms has shifted from an initial emphasis on astrocyte-arteriole-level processes to mechanisms that operate on the capillary level, a shift that has brought into sharp focus questions regarding the fine control of blood distribution to active neurons. As these investigations have drilled down into finer reaches of the microvasculature, they have revealed an arteriole-proximate subregion of CNS capillary networks that serves a regulatory function in directing blood flow into and within downstream capillaries. They have also illuminated differences in researchers' perspectives on the vascular structures and identity of mural cells in this region that impart the vasomodulatory effects that control blood distribution. In this review, we highlight the regulatory role of a variably named region of the microvasculature, referred to here as the post-arteriole transition zone, in channeling blood flow within CNS capillary networks, and underscore the contribution of dynamically contractile perivascular mural cell - generally, but not universally, recognized as pericytes - to this function.
Topics: Arterioles; Capillaries; Microvessels; Pericytes; Brain
PubMed: 36751860
DOI: 10.1113/JP282246 -
Lancet (London, England) Jun 1947
Topics: Arterioles
PubMed: 20343554
DOI: 10.1016/s0140-6736(47)91398-6 -
Biology of Sex Differences Jan 2019The pathogenesis of hypertension is distinct between men and women. Endothelin-1 (ET-1) is a potential contributor to sex differences in the pathophysiology of...
BACKGROUND
The pathogenesis of hypertension is distinct between men and women. Endothelin-1 (ET-1) is a potential contributor to sex differences in the pathophysiology of hypertension. ET-1 participates in blood pressure regulation through activation of endothelin A (ET) and endothelin B (ET) receptors including those in the vasculature. Previous studies demonstrated that sex and sex hormones evoke discrepancies in ET-1-mediated control of vascular tone in different vascular beds. However, little is known about sex- and sex hormone-related differences in ET-1-dependent renal microvascular reactivity. Accordingly, we hypothesized that loss of sex hormones impairs afferent arteriole reactivity to ET-1.
METHODS
Male and female Sprague Dawley rats were subjected to gonadectomy or sham surgery (n = 6/group). After 3 weeks, kidneys from those rats were prepared for assessment of renal microvascular responses to ET-1 (ET and ET agonist, 10 to 10 M) and sarafotoxin 6c (S6c, ET agonist, 10 to 10 M) using the blood-perfused juxtamedullary nephron preparation.
RESULTS
Control afferent arteriole diameters at 100 mmHg were similar between sham male and female rats averaging 14.6 ± 0.3 and 15.3 ± 0.3 μm, respectively. Gonadectomy had no significant effect on control arteriole diameter. In sham males, ET-1 produced significant concentration-dependent decreases in afferent arteriole diameter, with 10 M ET-1 decreasing diameter by 84 ± 1%. ET-1 induced similar concentration-dependent vasoconstrictor responses in sham female rats, with 10 M ET-1 decreasing the diameter by 82 ± 1%. The afferent arteriolar vasoconstrictor responses to ET-1 were unchanged by ovariectomy or orchiectomy. Selective ET receptor activation by S6c induced a concentration-dependent decline in afferent arteriole diameter, with 10 M S6c decreasing diameter by 77 ± 3 and 76 ± 3% in sham male and female rats, respectively. Notably, ovariectomy augmented the vasoconstrictor response to S6c (10 to 10 M), whereas orchiectomy had no significant impact on the responsiveness to ET receptor activation.
CONCLUSION
These data demonstrate that sex does not significantly influence afferent arteriole reactivity to ET receptor activation. Gonadectomy potentiated the responsiveness of the afferent arteriole to ET-induced vasoconstriction in females, but not males, suggesting that female sex hormones influence ET-mediated vasoconstriction in the renal microcirculation.
Topics: Animals; Arterioles; Castration; Endothelin-1; Female; Male; Microcirculation; Rats, Sprague-Dawley; Receptor, Endothelin A; Receptor, Endothelin B; Sex Characteristics; Vasoconstriction; Vasoconstrictor Agents; Viper Venoms
PubMed: 30606254
DOI: 10.1186/s13293-018-0218-2 -
Nephrology, Dialysis, Transplantation :... Oct 2006
Review
Topics: Animals; Arterioles; Humans; Juxtaglomerular Apparatus; Kidney; Models, Biological; Renin; Vascular Endothelial Growth Factor A
PubMed: 16854849
DOI: 10.1093/ndt/gfl308 -
Kidney International. Supplement Jun 1991Tubuloglomerular feedback (TGF) is generally regarded as being mediated by a single, humoral vasoconstrictor acting on the afferent arteriole. Examination of the... (Review)
Review
Tubuloglomerular feedback (TGF) is generally regarded as being mediated by a single, humoral vasoconstrictor acting on the afferent arteriole. Examination of the literature reveals, however, that acute activation or blockade of TGF may, under certain circumstances, be associated with vasomotion of the efferent arteriole, either in the same or in the opposite direction as the afferent arteriole. The former appears to be the case particularly when myogenic autoregulation is attenuated, for example, with application of calcium channel blockers. Experiments in which the TGF signal is chronically lost by preventing tubular fluid flow at the macula densa also suggest participation of the efferent arteriole. Under these circumstances, stop flow pressure and single nephron filtration rate increase and glomerular blood flow falls. TGF activity at this stage is modestly enhanced. Taken together, these findings suggest efferent vasoconstriction. After a delay of some hours, vasoconstriction is also apparent in the afferent arteriole. It is not clear whether the mechanism involved in this response is related to the "normal" TGF response. Together, these findings are hard to reconcile with the hypothesis of a single vasoconstrictor acting on the afferent arteriole.
Topics: Animals; Arterioles; Feedback; Kidney Glomerulus; Kidney Tubules; Vascular Resistance; Vasoconstriction
PubMed: 1881055
DOI: No ID Found -
Acta Physiologica (Oxford, England) Jun 2014
Topics: Animals; Arterioles; Coronary Vessels; Histocytological Preparation Techniques; Male; Organ Culture Techniques; Rats; Rats, Wistar; Sepharose
PubMed: 24698112
DOI: 10.1111/apha.12293 -
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 -
Experimental Eye Research Apr 2019Dysfunctional vascular endothelial nitric oxide synthase (eNOS) has been proposed to play a main pathophysiological role in various ocular diseases. The aim of the...
Dysfunctional vascular endothelial nitric oxide synthase (eNOS) has been proposed to play a main pathophysiological role in various ocular diseases. The aim of the present study was to test the hypothesis that the chronic lack of eNOS impairs endothelium-dependent vasodilation in retinal arterioles. The relevance of eNOS for mediating vascular responses was studied in retinal vascular preparations from eNOS-deficient mice (eNOS-/-) and wild-type controls in vitro. Changes in luminal diameter in response to vasoactive agents were measured by videomicroscopy. The thromboxane mimetic, U46619, induced similar concentration-dependent constriction of retinal arterioles in eNOS-/- and wild-type mice. Responses to the endothelium-independent vasodilator, nitroprusside, did not differ between both mouse genotypes, either. In contrast, responses to the endothelium-dependent vasodilator, acetylcholine, were blunted in eNOS-/- mice. Non-isoform-selective blockade of either nitric oxide synthase (NOS) or cyclooxygenase (COX) alone did not affect responses to acetylcholine. However, combined blockade of both enzyme families markedly attenuated cholinergic vasodilation. Also, combined blockade of COX and neuronal NOS (nNOS) blunted acetylcholine-induced vasodilation, while combined COX and inducible NOS (iNOS) inhibition had no effect. Simultaneous NOS and COX-1 blockade did not affect cholinergic vasodilation, whereas combined NOS and COX-2 inhibition markedly reduced vasodilation to acetylcholine. These findings are the first to demonstrate that the chronic lack of eNOS is associated with moderate endothelial dysfunction in retinal arterioles. However, eNOS-deficiency is partially compensated by nNOS and COX-2 metabolites, which are reciprocally regulated.
Topics: Animals; Arterioles; Disease Models, Animal; Endothelium, Vascular; Gene Expression Regulation; Male; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type III; RNA; Retinal Artery; Retinal Diseases; Vasodilation
PubMed: 30716330
DOI: 10.1016/j.exer.2019.01.022 -
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 -
Biomechanics and Modeling in... Jun 2019An increase in arterial pressure within the cerebral vasculature appears to coincide with ischemia and dysfunction of the neurovascular unit in some cases of traumatic...
An increase in arterial pressure within the cerebral vasculature appears to coincide with ischemia and dysfunction of the neurovascular unit in some cases of traumatic brain injury. In this study, we examine a new mechanism of brain tissue damage that results from excessive cerebral arteriole pressurization. We begin by considering the morphological and material properties of normotensive and hypertensive arterioles and present a computational model that captures the interaction of neighboring pressurized arterioles and the surrounding brain tissue. Assuming an axonal strain-induced injury criterion, we find that the injury depends on vessel spacing, proximity to an unconfined free surface, and the relative difference in stiffness between the arterioles and the surrounding tissue. We find that a steeper heterogeneity (stiffer vessels surrounded by softer brain tissue) causes larger axial strains to develop at some distance from the arteriole wall, within the brain parenchyma. For a more gradual heterogeneity (softer vessels), we observe more larger strain fields close to the arteriole walls. Both deformation patterns are comparable to damage seen in previous pathology studies on postmortem TBI patients. Finally, we use an analytical model to approximate the interplay between internal pressure, arteriole thickness, and the variation in mechanical properties of arterioles.
Topics: Animals; Anisotropy; Arterial Pressure; Arterioles; Brain; Brain Injuries, Traumatic; Cerebral Cortex; Computer Simulation; Elastic Modulus; Finite Element Analysis; Humans; Models, Biological; Rats; Stress, Mechanical
PubMed: 30604301
DOI: 10.1007/s10237-018-01107-z