Substance P increases microvascular permeability via nitric oxide-mediated convective pathways

The goal of these studies was to examine the effects of substance P, a tachykinin neuropeptide, on pathways of microvascular permeability. Individual frog mesenteric venular capillaries were cannulated, and albumin apparent permeability coefficients (Ps) were determined by quantitative fluorescence microscopy. Ps of albumin (PsAlb) rose from 6.8 +/- 1.8 (SE) cm.s-1.10(7) at control to 22.3 +/- 2.3 cm.s-1.10(7) when substance P (10(-11) M) was perfused. The effect of increased microvessel permeability induced by substance P (10(-11) M) was blocked with the nonpeptide substance P receptor antagonist CP-96,345 and NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. PsAlb increased 0.99 cm.s-1.10(7) for every cmH2O increase in microvessel pressure after treatment of the vessel with substance P, demonstrating coupling of albumin flux to transvascular water flow. In conclusion, the mechanism of increased microvessel permeability in response to substance P appears to be the result of receptor-mediated increase in nitric oxide production and formation of water-filled convective pathways presumably located between adjacent endothelial cells.

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Hypoxia activates nitric oxide synthase and stimulates nitric oxide production in porcine coronary resistance arteriolar endothelial cells

Cardiovascular Research ◽

10.1016/0008-6363(95)00117-4 ◽

1995 ◽

Vol 30 (6) ◽

pp. 841-847 ◽

Cited By ~ 25

Author(s):

X XU

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Nitric Oxide Synthase ◽

Nitric Oxide Production ◽

Coronary Resistance ◽

Oxide Production ◽

Oxide Synthase

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Retinoic acid decreases nitric oxide production in endothelial cells: a role of phosphorylation of endothelial nitric oxide synthase at Ser1179

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2004.11.099 ◽

2005 ◽

Vol 326 (4) ◽

pp. 703-710 ◽

Cited By ~ 13

Author(s):

Du-Hyong Cho ◽

Yoon Jung Choi ◽

Sangmee Ahn Jo ◽

Jae-Hwan Nam ◽

Sung-Chul Jung ◽

...

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Retinoic Acid ◽

Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

Nitric Oxide Production ◽

Oxide Production ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

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Endothelial nitric oxide synthase protein distribution and nitric oxide production in endothelial cells along the coronary vascular tree

Microvascular Research ◽

10.1016/j.mvr.2018.11.004 ◽

2019 ◽

Vol 122 ◽

pp. 34-40 ◽

Cited By ~ 1

Author(s):

Cristine L. Heaps ◽

Jeffrey F. Bray ◽

Avery L. McIntosh ◽

Friedhelm Schroeder

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

Nitric Oxide Production ◽

Protein Distribution ◽

Vascular Tree ◽

Oxide Production ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

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Vasoactive hormones induce nitric oxide synthase mRNA expression and nitric oxide production in human endothelial cells and monocytes

American Journal of Hypertension ◽

10.1016/s0895-7061(98)00254-4 ◽

1999 ◽

Vol 12 (4) ◽

pp. 388-397 ◽

Cited By ~ 17

Author(s):

M Schena

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Nitric Oxide Synthase ◽

Mrna Expression ◽

Nitric Oxide Production ◽

Human Endothelial Cells ◽

Oxide Production ◽

Vasoactive Hormones ◽

Oxide Synthase

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122 Substance P Induce Nitric Oxide Production in Human Microvascular Endothelial Cells

Wound Repair and Regeneration ◽

10.1111/j.1067-1927.2005.130216z.x ◽

2008 ◽

Vol 13 (2) ◽

pp. A28-A48 ◽

Cited By ~ 1

Author(s):

P Muangman ◽

L.A. Muffley ◽

N.S. Gibran

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Substance P ◽

Microvascular Endothelial Cells ◽

Nitric Oxide Production ◽

Oxide Production ◽

Microvascular Endothelial

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Nitric oxide production in human endothelial cells stimulated by histamine requires Ca2+ influx

Biochemical Journal ◽

10.1042/bj3300695 ◽

1998 ◽

Vol 330 (2) ◽

pp. 695-699 ◽

Cited By ~ 90

Author(s):

Frédérique LANTOINE ◽

Lahcen IOUZALEN ◽

Marie-Aude DEVYNCK ◽

Elisabeth MILLANVOYE-van BRUSSEL ◽

Monique DAVID-DUFILHO

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

No Production ◽

Nitric Oxide Production ◽

Human Endothelial Cells ◽

Indirect Methods ◽

No Release ◽

K Concentration ◽

Internal Side ◽

Oxide Synthase

The causal relationships between cytosolic free-Ca2+ concentration ([Ca2+]i) increases and production of nitric oxide (NO) have been investigated mostly with indirect methods and remain unclear. Here we demonstrate, by direct real-time measurements of [NO] with a porphyrinic microsensor, that Ca2+ entry, but not an increase in [Ca2+]i, is required for triggering of NO production in human endothelial cells. Histamine, ranging from 0.1 to 100 μM, increased both NO production and [Ca2+]i when given in a single dose. However, histamine caused increased NO release but induced progressively smaller [Ca2+]i changes when cumulatively added. In the absence of a transmembrane Ca2+ gradient, no significant NO release was detectable, despite the marked Ca2+ peak induced by histamine. Inhibition of Ca2+ entry by SK&F 96365 abolished histamine-elicited NO production but only reduced the transient [Ca2+]i rise. The suppression of the sustained [Ca2+]i response under these two conditions suggests that NO release was closely associated with Ca2+ entry from the extracellular space. In addition, membrane depolarization, achieved by increasing the extracellular K+ concentration from 5 to 130 mM, reduced both the amplitude of histamine-induced sustained [Ca2+]i elevation and NO production. These results lead us to propose that the availability of numerous Ca2+ ions around the internal side of the plasma membrane would promote the association between nitric oxide synthase and calmodulin, thereby activating the enzyme.

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