scholarly journals Brain capillary pericytes exert a substantial but slow influence on blood flow

2020 ◽  
Author(s):  
David A. Hartmann ◽  
Andrée-Anne Berthiaume ◽  
Roger I. Grant ◽  
Sarah A. Harrill ◽  
Tegan Noonan ◽  
...  
Keyword(s):  
Blood Flow ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Two Photon Microscopy ◽  
Capillary Networks ◽  
Mural Cells ◽  
Complementary Approach ◽  
Blood Flow Control ◽  
Capillary Bed

The majority of the brain’s vasculature is comprised of intricate capillary networks lined by capillary pericytes. However, it remains unclear whether capillary pericytes contribute to blood flow control. Using two-photon microscopy to observe and manipulate single capillary pericytes in vivo, we find their optogenetic stimulation decreases lumen diameter and blood flow, but with slower kinetics than mural cells of upstream pial and pre-capillary arterioles. This slow, optogenetically-induced vasoconstriction was inhibited by the clinically-used vasodilator fasudil, a Rho kinase inhibitor that blocks contractile machinery. Capillary pericytes were also slower to constrict back to baseline following hypercapnia-induced dilation, and relax towards baseline following optogenetically-induced vasoconstriction. In a complementary approach, optical ablation of single capillary pericytes led to sustained local dilation and a doubling of blood cell flux in capillaries lacking pericyte contact. Altogether these data indicate that capillary pericytes contribute to basal blood flow resistance and slow modulation of blood flow throughout the capillary bed.

Rho kinase regulates renal blood flow by modulating eNOS activity in ischemia-reperfusion of the rat kidney

2006 ◽  
Vol 291 (3) ◽  
pp. F606-F611 ◽  
Author(s):  
Amanda M. G. Versteilen ◽  
Iolente J. M. Korstjens ◽  
René J. P. Musters ◽  
A. B. Johan Groeneveld ◽  
Pieter Sipkema
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Renal Blood Flow ◽  
Kinase Inhibitor ◽  
Ex Vivo ◽  
Rat Kidney ◽  
Ischemia Reperfusion ◽  
Rho Kinase ◽  
Rho Kinase Inhibitor

Renal ischemia-reperfusion (I/R) results in vascular dysfunction characterized by a reduced endothelium-dependent vasodilatation and subsequently impaired blood flow. In this study, we investigated the role of Rho kinase in endothelial nitric oxide synthase (eNOS)-mediated regulation of renal blood flow and vasomotor tone in renal I/R. Male Wistar rats were subjected to 60-min bilateral clamping of the renal arteries or sham procedure. One hour before the clamping, the Rho kinase inhibitor Y27632 (1 mg/kg) was intravenously infused. After I/R, renal blood flow was measured using fluorescent microspheres. I/R resulted in a 62% decrease in renal blood flow. In contrast, the blood flow decrease in the group treated with the Rho kinase inhibitor (YI/R) was prevented. Endothelium-dependent vasodilatation of renal arcuate arteries to ACh was measured ex vivo in a pressure myograph. These experiments demonstrated that the in vivo treatment with the Rho kinase inhibitor prevented the decrease in the nitric oxide (NO)-mediated vasodilator response. In addition, after I/R renal interlobar arteries showed a decrease in phosphorylated eNOS and vasodilator-stimulated phosphoprotein, a marker for bioactive NO, which was attenuated by in vivo Rho kinase inhibition. These findings indicate that in vivo inhibition of Rho kinase in renal I/R preserves renal blood flow by improving eNOS function.

scholarly journals Imaging the construction of capillary networks in the neonatal mouse brain

2021 ◽  
Vol 118 (26) ◽  
pp. e2100866118
Author(s):  
Vanessa Coelho-Santos ◽  
Andrée-Anne Berthiaume ◽  
Sharon Ornelas ◽  
Heidi Stuhlmann ◽  
Andy Y. Shih
Keyword(s):  
Blood Flow ◽  
Brain Diseases ◽  
Brain Capillary ◽  
Capillary Networks ◽  
Two Photon ◽  
Capillary Bed ◽  
Flow Through ◽  
And Function ◽  
Blood Brain Barrier Integrity

Capillary networks are essential for distribution of blood flow through the brain, and numerous other homeostatic functions, including neurovascular signal conduction and blood–brain barrier integrity. Accordingly, the impairment of capillary architecture and function lies at the root of many brain diseases. Visualizing how brain capillary networks develop in vivo can reveal innate programs for cerebrovascular growth and repair. Here, we use longitudinal two-photon imaging through noninvasive thinned skull windows to study a burst of angiogenic activity during cerebrovascular development in mouse neonates. We find that angiogenesis leading to the formation of capillary networks originated exclusively from cortical ascending venules. Two angiogenic sprouting activities were observed: 1) early, long-range sprouts that directly connected venules to upstream arteriolar input, establishing the backbone of the capillary bed, and 2) short-range sprouts that contributed to expansion of anastomotic connectivity within the capillary bed. All nascent sprouts were prefabricated with an intact endothelial lumen and pericyte coverage, ensuring their immediate perfusion and stability upon connection to their target vessels. The bulk of this capillary expansion spanned only 2 to 3 d and contributed to an increase of blood flow during a critical period in cortical development.

scholarly journals Hydrogel Tissue Construct-Based High-Content Compound Screening

2010 ◽  
Vol 16 (1) ◽  
pp. 120-128 ◽  
Author(s):  
Vy Lam ◽  
Tetsuro Wakatsuki
Keyword(s):  
Kinase Inhibitor ◽  
Physiological Mechanism ◽  
Rho Kinase ◽  
Assay System ◽  
Physiological Status ◽  
Multiple Parameters ◽  
Compound Screening ◽  
Tissue Construct

Current pharmaceutical compound screening systems rely on cell-based assays to identify therapeutic candidates and potential toxicities. However, cells grown on 2D substrata or in suspension do not exhibit the mechanical or physiological properties of cells in vivo. To address this limitation, the authors developed an in vitro, high-throughput, 3D hydrogel tissue construct (HTC)–based assay system to quantify cell and tissue mechanical properties and multiple parameters of physiology. HTC mechanics was quantified using an automated device, and physiological status was assessed using spectroscopy-based indicators that were read on microplate readers. To demonstrate the application of this system, the authors screened 4 test compounds—rotenone (ROT), cytochalasin D (CD), 2,4-dinitrophenol (DNP), and Rho kinase inhibitor (H-1152)—for their ability to modulate HTC contractility without affecting actin integrity, mitochondrial membrane potential (MMP), or viability. All 4 compounds dose-dependently reduced HTC contractility. However, ROT was toxic, DNP dissipated MMP, and CD reduced both intracellular F-actin and viability. H-1152 was found to be the best candidate compound since it reduced HTC contractility with minimal side effects. The authors propose that their HTC-based assay system can be used to screen for compounds that modulate HTC contractility and assess the underlying physiological mechanism(s) of compound activity and toxicity.

scholarly journals Rho-kinase inhibitor, fasudil, suppresses glioblastoma cell line progression in vitro and in vivo

2010 ◽  
Vol 9 (11) ◽  
pp. 875-884 ◽  
Author(s):  
Lin Deng ◽  
Gang Li ◽  
Ronghui Li ◽  
Qinglin Liu ◽  
Qiaowei He ◽  
...  
Keyword(s):  
Cell Line ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Glioblastoma Cell Line ◽  
Glioblastoma Cell ◽  
Rho Kinase Inhibitor

Rho-Kinase Inhibitor Retards Migration and in Vivo Dissemination of Human Prostate Cancer Cells

2000 ◽  
Vol 269 (3) ◽  
pp. 652-659 ◽  
Author(s):  
Avril V. Somlyo ◽  
Dawn Bradshaw ◽  
Susan Ramos ◽  
Cheryl Murphy ◽  
Charles E. Myers ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Rho Kinase Inhibitor

Blood flow in the ovary and adjacent structures of the non-pregnant sheep

1983 ◽  
Vol 103 (2) ◽  
pp. 259-265 ◽  
Author(s):  
P. O. Janson ◽  
D. Williams ◽  
O. M. Petrucco ◽  
F. Amato ◽  
R. F. Seamark ◽  
...  
Keyword(s):  
Blood Flow ◽  
Venous Blood ◽  
Vascular Pedicle ◽  
Venous Flow ◽  
Adjacent Structures ◽  
Pregnant Sheep ◽  
Rapid Changes ◽  
Capillary Bed

Abstract. Blood flow to the ovary, vascular pedicle and oviduct was measured in anaesthetized non-cycling and cycling ewes by timed collection of ovarian venous blood. The degree of arterio-venous shunting across the ovary and pedicle was estimated both in vivo and in vitro by perfusing the tissues with 15 ± 5 μm radioactive microspheres. The mean ovarian blood flow in non-cycling animals was 1.9 ml/min, which was 51% of blood flow in the ovarian vein. In cycling animals ovarian blood flow at midcycle was 2.9 ml/min (66% of ovarian venous flow) in non-luteal ovaries and 4.3 ml/min (79% of venous flow) in luteal ovaries. The degree of arterio-venous shunting was low in all stages of the cycle (1.0–2.6% across ovary + pedicle). The degree of shunting was also found to be very small in vitro (0.007–1.38%) in both non-luteal and luteal ovaries. A considerable number of microspheres was entrapped in the vascular pedicle of the ovary indicating the presence of an extensive capillary bed. There was an inverse relationship between blood flow in the ovary and flow in the vascular pedicle. Alterations in distribution of blood flow between the ovary and adjacent structures supplied by the ovarian artery may be of functional significance in allowing rapid changes in ovarian blood flow. The results of the present study indicate that changes in ovarian blood flow during the oestrous cycle are not caused by an action on arteriovenous shunt vessels.

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