scholarly journals Novel Functional Aspect of Antihistamines: The Impact of Bepotastine Besilate on Substance P-Induced Events

2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Shun Kitaba ◽  
Hiroyuki Murota ◽  
Yoko Yahata ◽  
Hiroaki Azukizawa ◽  
Ichiro Katayama
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Substance P ◽  
Adhesion Molecules ◽  
Skin Diseases ◽  
Mast Cell Degranulation ◽  
Microvascular Endothelial Cells ◽  
Functional Aspect ◽  
The Impact ◽  
Pruritic Skin

Besides histamine, substance P (SP) has been demonstrated to play a crucial role in pruritic skin diseases. Although antihistamines are frequently used for pruritic skin diseases, little is known concerning the effect on an SP-induced event such as mast cell degranulation and the upregulation of adhesion molecules or the nitric oxide (NO) synthesis in endothelial cells. Our aim was to study the effect of bepotastine besilate on SP-induced degranulation of rat basophillic leukemia (RBL-2H3) cells and expression of adhesion molecules and NO synthesis in human dermal microvascular endothelial cells (HMVECs). Bepotastine besilate significantly inhibited SP-induced degranulation of RBL-2H3 cells and NO synthesis in HMVECs. Bepotastine besilate significantly inhibited expression of adhesion molecules in HMVESs, while it failed to suppress SP-induced upregulation of the adhesion molecules in HMVECs. Therefore, bepotastine besilate is assumed to act favorably on SP-induced basophil degranulation and NO synthesis in HMVECs.

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

1995 ◽  
Vol 268 (4) ◽  
pp. R1060-R1068 ◽  
Author(s):  
L. S. Nguyen ◽  
A. C. Villablanca ◽  
J. C. Rutledge
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Substance P ◽  
Microvascular Permeability ◽  
Nitric Oxide Production ◽  
Apparent Permeability ◽  
Substance P Receptor ◽  
Microvessel Permeability ◽  
Oxide Synthase ◽  
Quantitative Fluorescence

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.

Abstract 18331: Endothelial Microrna-155 Promotes Myocardial Microvascular Permeability and Inflammatory Cell Adhesion in Experimental Septic Cardiomyopathy

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Francisco Vasques-Nóvoa ◽  
Catarina Quina-Rodrigues ◽  
Rui Cerqueira ◽  
Fabiana Baganha ◽  
Tiago L Laundos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Inflammatory Cell ◽  
Septic Cardiomyopathy ◽  
Nitric Oxide Production ◽  
Monocyte Adhesion ◽  
Cytokine Mrna ◽  
Vasp Phosphorylation ◽  
Mrna Profile

Introduction: Septic cardiomyopathy remains a leading cause of death in critically ill patients. Myocardial edema and inflammatory cell recruitment to cardiac interstitial space are proposed mechanisms underlying sepsis-induced contractile dysfunction. Hypothesis: Evaluate the role of endothelial microRNA-155 (miR-155) in experimental septic cardiomyopathy. Methods: Experimental sepsis was induced using LPS injection in WT (n=20) and miR-155-/- (KO; n=20) male mice. Cardiac function was evaluated through echocardiography. Expression of NOS2, NOS3, VASP phosphorylation and myocardial nitrite/nitrate content was evaluated. Cardiac microvascular (MV) permeability was assessed with evans blue-albumin conjugate leaking to extravascular space and myocardial water content. Mouse cardiac MV endothelial cells (MCMVEC; CD31+Sca-1+CD45-) were isolated with FACS. Quantification of miR-155, cytokine mRNA profile and adhesion molecules (ICAM1, VCAM1 and E-selectin) was performed. Human cardiac MV endothelial cells (HCMVEC) were transfected with anti-miR-155 or scramble LNA probe and incubated with LPS (100ng/mL) or vehicle for 24h. Evaluation of cytokine mRNA profile, NOS isoforms, VASP phosphorylation and adhesion molecules was performed. Monocyte adhesion assay was performed using Dil-stained THP1 monocytic cells. Results: LPS exposure increased miR-155 expression in the myocardium, MCMVEC and HCMVEC. KO mice presented with attenuated LPS-induced cardiac dysfunction, MV permeability, NOS2 expression and VASP phosphorylation, compared with WT. KO MCMVEC presented with attenuated LPS-induced cytokine expression and adhesion molecules, compared with WT cells. Mir-155 inhibition in HCMVEC prevented LPS-induced overexpression of cytokines and adhesion molecules, nitric oxide production and monocyte adhesion, through SOCS1-mediated inhibition of STAT3 and NF-kB signaling pathways. Conclusions: Endothelial miR-155 is upregulated in experimental septic cardiomyopathy. MiR-155 knockout attenuates LPS-induced myocardial dysfunction, edema and MV permeability. In MCMVEC and HCMVEC, miR-155 inhibition blunted LPS-induced nitric oxide production, cytokine and cell adhesion molecules overexpression.

scholarly journals Lipoic acid antagonizes paraquat-induced vascular endothelial dysfunction by suppressing mitochondrial reactive oxidative stress

2019 ◽  
Vol 8 (6) ◽  
pp. 918-927 ◽  
Author(s):  
Li Pang ◽  
Ping Deng ◽  
Yi-dan Liang ◽  
Jing-yu Qian ◽  
Li-Chuan Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Lipoic Acid ◽  
Microvascular Endothelial Cells ◽  
Ros Generation ◽  
Protective Effects ◽  
Migration Ability ◽  
Microvascular Endothelial

Abstract Paraquat (PQ) is a widely used herbicide in the agricultural field. The lack of an effective antidote is the significant cause of high mortality in PQ poisoning. Here, we investigate the antagonistic effects of alpha lipoic acid (α-LA), a naturally existing antioxidant, on PQ toxicity in human microvascular endothelial cells (HMEC-1). All the doses of 250, 500 and 1000 μM α-LA significantly inhibited 1000 μM PQ-induced cytotoxicity in HMEC-1 cells. α-LA pretreatment remarkably diminished the damage to cell migration ability, recovered the declined levels of the vasodilator factor nitric oxide (NO), elevated the expression level of endothelial nitric oxide synthases (eNOS), and inhibited the upregulated expression of vasoconstrictor factor endothelin-1 (ET-1). Moreover, α-LA pretreatment inhibited reactive oxygen species (ROS) generation, suppressed the damage to the mitochondrial membrane potential (ΔΨm) and mitigated the inhibition of adenosine triphosphate (ATP) production in HMEC-1 cells. These results suggested that α-LA could alleviate PQ-induced endothelial dysfunction by suppressing oxidative stress. In summary, our present study provides novel insight into the protective effects and pharmacological potential of α-LA against PQ toxicity in microvascular endothelial cells.

Differential expression of nitric oxide by dermal microvascular endothelial cells from patients with scleroderma

2000 ◽  
Vol 5 (3) ◽  
pp. 147-158 ◽  
Author(s):  
L.I. Romero ◽  
D-N. Zhang ◽  
J.P. Cooke ◽  
H-K. V Ho ◽  
E. Avalos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Differential Expression ◽  
Microvascular Endothelial Cells ◽  
Microvascular Endothelial
Sign in / Sign up

Export Citation Format

Share Document