The Capillary Bed in Nonspecific Endotoxoid-Induced Endotoxin Tolerance

Nitric oxide (NO) has been shown to be a potent vasodilator released from endothelial cells (EC) in large blood vessels, but NO release has not been examined in the capillary bed. Because the capillary bed represents the largest source of EC, it may be the largest source of vascular NO. In the present study, we used intravital microscopy to examine the effect of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on the microvasculature of the rat extensor digitorum longus muscle. L-NAME (30 mM) applied locally to a capillary (300 micron(s) from the feeding arteriole) reduced red blood cell (RBC) velocity [VRBC; control VRBC = 238 +/- 58 (SE) micron/s; delta VRBC = -76 +/- 8%] and RBC flux (4.4 +/- 0.7 to 2.8 +/- 0.7 RBC/s) significantly in the capillary, but did not change feeding arteriole diameter (Dcon = 6.3 +/- 0.7 micron, delta D = 5 +/- 7%) or draining venule diameter (Dcon = 10.1 +/- 0.6 micron, delta D = 4 +/- 2%). Because of the VRBC change, the flux reduction was equivalent to an increased local hemoconcentration from 1.8 to 5 RBCs per 100 micron capillary length. L-NAME also caused an increase in the number of adhering leukocytes in the venule from 0.29 to 1.43 cells/100 micron. L-NAME (30 mM) applied either to arterioles or to venules did not change capillary VRBC. Bradykinin (BK) locally applied to the capillary caused significant increases in VRBC (delta VRBC = 111 +/- 23%) and in arteriolar diameter (delta D = 40 +/- 5%). This BK response was blocked by capillary pretreatment with 30 mM L-NAME (delta VRBC = -4 +/- 27%; delta D = 5 +/- 9% after BK). We concluded that NO may be released from capillary EC both basally and in response to the vasodilator BK. We hypothesize that 1) low basal levels of NO affect capillary blood flow by modulating local hemoconcentration and leukocyte adhesion, and 2) higher levels of NO (stimulated by BK) may cause a remote vasodilation to increase microvascular blood flow.

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Vascularized organoids on a chip: strategies for engineering organoids with functional vasculature

Lab on a Chip ◽

10.1039/d0lc01186j ◽

2021 ◽

Vol 21 (3) ◽

pp. 473-488

Author(s):

Shun Zhang ◽

Zhengpeng Wan ◽

Roger D. Kamm

Keyword(s):

Capillary Bed

Possible strategy to integrate pre-vascularized organoid and in vitro capillary bed on a microfluidic based platform, aiming for establishing perfused vasculature throughout organoids in vitro.

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Adiponectin Mediates Endotoxin Tolerance in Lung.

10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a3738 ◽

2009 ◽

Author(s):

J Konter ◽

D Dwyer ◽

S Natarajan ◽

D Remick ◽

A Fine ◽

...

Keyword(s):

Endotoxin Tolerance

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Reduced Ex Vivo Interleukin-8 Production by Neutrophils in Septic and Nonseptic Systemic Inflammatory Response Syndrome

Blood ◽

10.1182/blood.v91.9.3439 ◽

1998 ◽

Vol 91 (9) ◽

pp. 3439-3446 ◽

Cited By ~ 79

Author(s):

Christelle Marie ◽

Jane Muret ◽

Catherine Fitting ◽

Marie-Reine Losser ◽

Didier Payen ◽

...

Keyword(s):

Systemic Inflammatory Response Syndrome ◽

Inflammatory Response ◽

Ex Vivo ◽

Endotoxin Tolerance ◽

Systemic Inflammatory Response ◽

Interleukin 8 ◽

Polymorphonuclear Cells ◽

Healthy Controls ◽

Relative Contribution

AbstractEx vivo cytokine production by circulating lymphocytes and monocytes is reduced in patients with infectious or noninfectious systemic inflammatory response syndrome. Very few studies have addressed the reactivity of polymorphonuclear cells (PMN). To analyze further the relative contribution of systemic inflammatory response syndrome alone or in combination with infection we studied the interleukin-8 (IL-8) production by PMN isolated from patients who had undergone cardiac surgery with cardiopulmonary bypass (CPB) and patients with sepsis. Cells were activated with either lipopolysaccharide (LPS) or heat-killed streptococci. Compared with healthy controls, the release of IL-8 by PMN in both groups of patients was significantly reduced whether activated by LPS, independently of its concentration and origin, or by heat-killed streptococci. These observations suggest that stressful conditions related to inflammation, independently of infection, rapidly dampened the reactivity of circulating PMN. We investigated whether the observed diminished reactivity of PMN might reflect an endotoxin tolerance phenomenon. Our in vitro experiments with PMN from healthy controls indicated that PMN could not be rendered tolerant stricto sensu. However, our data suggested that LPS-induced mediators such as IL-10 may be responsible for the observed anergy in patients.

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