Precapillary sphincters and pericytes at first-order capillaries as key regulators for brain capillary perfusion
Autor: | Martin Lauritzen, Reena Murmu Nielsen, Micael Lønstrup, Jingshi Hu, Birger Brodin, Jonas C. Fordsmann, Changsi Cai, Hans Christian Cederberg Helms, Stefan Andreas Zambach, Bjørn Olav Hald, Yiqiu Dong |
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Rok vydání: | 2021 |
Předmět: |
Vascular smooth muscle
Endothelium S-Nitroso-N-Acetylpenicillamine Nitric Oxide Nitric oxide chemistry.chemical_compound Mice KATP Channels Ischemia medicine Pressure Animals Nitric Oxide Donors Cyclic guanosine monophosphate Cyclic GMP Multidisciplinary Endothelin-1 Receptors Endothelin Brain Blood flow Biological Sciences Potassium channel Acetylcholine Capillaries Perfusion Vasodilation medicine.anatomical_structure Cerebral blood flow chemistry Biophysics Endothelium Vascular Nitric Oxide Synthase Pericytes Ion Channel Gating medicine.drug |
Zdroj: | Proc Natl Acad Sci U S A Zambach, S A, Cai, C, Helms, H C C, Hald, B O, Dong, Y, Fordsmann, J C, Nielsen, R M, Hu, J, Lønstrup, M, Brodin, B & Lauritzen, M J 2021, ' Precapillary sphincters and pericytes at first-order capillaries as key regulators for brain capillary perfusion ', Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 26, e2023749118 . https://doi.org/10.1073/pnas.2023749118 |
ISSN: | 1091-6490 |
Popis: | Rises in local neural activity trigger local increases of cerebral blood flow, which is essential to match local energy demands. However, the specific location of microvascular flow control is incompletely understood. Here, we used two-photon microscopy to observe brain microvasculature in vivo. Small spatial movement of a three-dimensional (3D) vasculature makes it challenging to precisely measure vessel diameter at a single x-y plane. To overcome this problem, we carried out four-dimensional (x-y-z-t) imaging of brain microvessels during exposure to vasoactive molecules in order to constrain the impact of brain movements on the recordings. We demonstrate that rises in synaptic activity, acetylcholine, nitric oxide, cyclic guanosine monophosphate, ATP-sensitive potassium channels, and endothelin-1 exert far greater effects on brain precapillary sphincters and first-order capillaries than on penetrating arterioles or downstream capillaries, but with similar kinetics. The high level of responsiveness at precapillary sphincters and first-order capillaries was matched by a higher level of α-smooth muscle actin in pericytes as compared to penetrating arterioles and downstream capillaries. Mathematical modeling based on 3D vasculature reconstruction showed that precapillary sphincters predominantly regulate capillary blood flow and pressure as compared to penetrating arterioles and downstream capillaries. Our results confirm a key role for precapillary sphincters and pericytes on first-order capillaries as sensors and effectors of endothelium- or brain-derived vascular signals. |
Databáze: | OpenAIRE |
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