In SituObservation of Living Pericytes in Rat Retinal Capillaries

Schönfelder, U.; Höfer, Andreas; Paul, Michael E.; Funk, Richard

doi:10.1006/mvre.1998.2086

Cited by 92 publications

(73 citation statements)

References 23 publications

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“…Paradoxically, the effects of diabetes on VDCC function in the circulatory system are variable. On the one hand, arteriolar L-type VDCC activity is attenuated in the kidney 30 and tail 31 of diabetic rats. On the other hand, VDCC activity appears to be increased in mesenteric, 32 skeletal, 33 and cerebral 34 arteriolar myocytes.…”

Section: Discussionmentioning

confidence: 99%

Diabetes-Induced Inhibition of Voltage-Dependent Calcium Channels in the Retinal Microvasculature: Role of Spermine

Matsushita

Fukumoto

Kobayashi

et al. 2010

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.Although decentralized control of blood flow is particularly important in the retina, knowledge of the functional organization of the retinal microvasculature is limited. Here, the authors characterized the distribution and regulation of L-type voltage-dependent calcium channels (VDCCs) within the most decentralized operational complex of the retinal vasculature-the feeder vessel/capillary unit-which consists of a capillary network plus the vessel linking it with a myocyteencircled arteriole. METHODS. Perforated-patch recordings, calcium-imaging, and time-lapse photography were used to assess VDCC-dependent changes in ionic currents, intracellular calcium, abluminal cell contractility, and lumen diameter, in microvascular complexes freshly isolated from the rat retina. RESULTS. Topographical heterogeneity was found in the distribution of functional VDCCs; VDCC activity was markedly greater in feeder vessels than in capillaries. Experiments showed that this topographical distribution occurs, in large part, because of the inhibition of capillary VDCCs by a mechanism dependent on the endogenous polyamine spermine. An operational consequence of functional VDCCs predominantly located in the feeder vessels is that voltage-driven vasomotor responses are generated chiefly in this portion of the feeder vessel/capillary unit. However, early in the course of diabetes, this ability to generate voltage-driven vasomotor responses becomes profoundly impaired because of the inhibition of feeder vessel VDCCs by a spermine-dependent mechanism. CONCLUSIONS. The regulation of VDCCs by endogenous spermine not only plays a critical role in establishing the physiological organization of the feeder vessel/capillary unit, but also may contribute to dysfunction of this decentralized operational unit in the diabetic retina. (Invest Ophthalmol Vis Sci.

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Section: Discussionmentioning

confidence: 99%

Diabetes-Induced Inhibition of Voltage-Dependent Calcium Channels in the Retinal Microvasculature: Role of Spermine

Matsushita

Fukumoto

Kobayashi

et al. 2010

Invest. Ophthalmol. Vis. Sci.

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“…Pericytes, the only cells associated with these vessels that express contractile proteins (Nehls and Drenckhahn 1991;Hughes and Chan-Ling 2004;Hamilton et al 2010), can actively dilate and constrict in response to vasoactive agents (Schonfelder et al 1998;Peppiatt et al 2006;Puro 2007;Hamilton et al 2010). Hall et al (2014) have shown that pericytes in the somatosensory cortex actively relax in response to whisker-pad stimulation.…”

Section: Regulation Of Blood Flow By Capillariesmentioning

confidence: 99%

Astrocyte Regulation of Blood Flow in the Brain

MacVicar

Newman

2015

Cold Spring Harb Perspect Biol

284

210

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Neuronal activity results in increased blood flow in the brain, a response named functional hyperemia. Astrocytes play an important role in mediating this response. Neurotransmitters released from active neurons evoke Ca 2þ increases in astrocytes, leading to the release of vasoactive metabolites of arachidonic acid from astrocyte endfeet onto blood vessels. Synthesis of prostaglandin E2 (PGE2) and epoxyeicosatrienoic acids (EETs) dilate blood vessels, whereas 20-hydroxyeicosatetraenoic acid (20-HETE) constricts vessels. The release of K þ from astrocyte endfeet may also contribute to vasodilation. Oxygen modulates astrocyte regulation of blood flow. Under normoxic conditions, astrocytic Ca 2þ signaling results in vasodilation, whereas under hyperoxic conditions, vasoconstriction is favored. Astrocytes also contribute to the generation of vascular tone. Tonic release of both 20-HETE and ATP from astrocytes constricts vascular smooth muscle cells, generating vessel tone. Under pathological conditions, including Alzheimer's disease and diabetic retinopathy, disruption of normal astrocyte physiology can compromise the regulation of blood flow.A strocytes have an intimate relationship with blood vessels in the brain as their endfoot processes completely envelop all cerebral blood vessels. The interplay between astrocyte endfeet and the cerebral vasculature is an area of intense investigation as work over the past 10 years has shown that astrocytes are involved in the regulation of cerebral blood flow (CBF). Matching CBF to the metabolic demands of brain activity is essential for healthy brain function. The maintenance of brain homeostasis and cognitive processing requires substantial energy expenditures relative to the rest of the human body. It is estimated that 20% of total body energy consumption is caused by brain activity, although the brain represents only 2% of the total body weight. Calculations of the brain energy budget have estimated that the greatest proportion of the energy expenditure in the brain is attributed to synaptic transmission (Howarth et al. 2012). This suggests that synaptic transmission will be preferentially impacted by reductions in the energy supply to the brain. Oxidative metabolism in the brain is almost exclusively owing to aerobic glycolysis, indicating that glucose and oxygen are the primary energy fuels in the brain (Magistretti et al. 2000). Therefore, the roles of astrocytes in reg-

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“…The contractility of cultured pericytes is well established and, of all organs, capillaries in the central nervous system (CNS) are endowed with the highest number of pericytes (4). Pericytes of the isolated retina have been shown to react to vasoactive substances (5). Recently, pericytes in cerebellar slice preparations were found to react with dilatations and constrictions to the application of different neurotransmitters, suggesting a general capacity of capillaries to increase blood supply locally (6).…”

mentioning

confidence: 99%

Pericytes in capillaries are contractile in vivo, but arterioles mediate functional hyperemia in the mouse brain

Fernández-Klett

Offenhauser²,

Dirnagl³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

351

346

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Modern functional imaging techniques of the brain measure local hemodynamic responses evoked by neuronal activity. Capillary pericytes recently were suggested to mediate neurovascular coupling in brain slices, but their role in vivo remains unexplored. We used two-photon microscopy to study in real time pericytes and the dynamic changes of capillary diameter and blood flow in the cortex of anesthetized mice, as well as in brain slices. The thromboxane A 2 analog, 9,11-dideoxy-9α,11α-methanoepoxy Prostaglandin F2α (U46619), induced constrictions in the vicinity of pericytes in a fraction of capillaries, whereas others dilated. The changes in vessel diameter resulted in changes in capillary red blood cell (RBC) flow. In contrast, during brief epochs of seizure activity elicited by local administration of the GABA A receptor antagonist, bicuculline, capillary RBC flow increased without pericyte-induced capillary diameter changes. Precapillary arterioles were the smallest vessels to dilate, together with penetrating and pial arterioles. Our results provide in vivo evidence that pericytes can modulate capillary blood flow in the brain, which may be important under pathological conditions. However, our data suggest that precapillary and penetrating arterioles, rather than pericytes in capillaries, are responsible for the blood flow increase induced by neural activity.cerebral blood flow | neurovascular coupling | cortical spreading depolarization | electrophysiology

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In SituObservation of Living Pericytes in Rat Retinal Capillaries

Cited by 92 publications

References 23 publications

Diabetes-Induced Inhibition of Voltage-Dependent Calcium Channels in the Retinal Microvasculature: Role of Spermine

Diabetes-Induced Inhibition of Voltage-Dependent Calcium Channels in the Retinal Microvasculature: Role of Spermine

Astrocyte Regulation of Blood Flow in the Brain

Pericytes in capillaries are contractile in vivo, but arterioles mediate functional hyperemia in the mouse brain

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