Nitric Oxide Mediates Microvascular Permeability in the Isolated Perfused Rat Mesentery?

Abstract Background: Positive pressure ventilation with large tidal volumes has been shown to cause lung injury via the serine/threonine kinase-protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS)-pathways. However, the effects of high tidal volume (VT) ventilation on the heart are unclear. Objectives: Evaluate the effect of VT ventilation on the cardiac vascular permeability and intracellular Akt and eNOS signaling pathway. Methods: C57BL/6 and Akt knock-out (heterozygotes, +/−) mice were exposed to high VT (30 mL/kg) mechanical ventilation with room air for one and/or five hours. Results: High VT ventilation increased cardiac microvascular permeability and eNOS phosphorylation in a timedependent manner. Serum cardiac troponin I was increased after one hour of high VT ventilation. Cardiac Akt phosphorylation was accentuated after one hour and attenuated after five hours of high VT ventilation. Pharmacological inhibition of Akt with LY294002 and high VT ventilation of Akt+/− mice attenuated cardiac Akt phosphorylation, but not eNOS phosphorylation. Conclusion: High VT ventilation increased cardiac myocardial injury, microvascular permeability, and eNOS phosphorylation. Involvement of cardiac Akt in high VT ventilation was transient.

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Endothelial nitric oxide synthase-derived NO signals regulate microvascular permeability

10.36866/pn.65.21 ◽

2007 ◽

pp. 21-23

Author(s):

Walter Durán ◽

Takuya Hatakeyama ◽

Fabiola Sánchez

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

Microvascular Permeability ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

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Lung microvascular permeability and neutrophil recruitment are differently regulated by nitric oxide in a rat model of intestinal ischemia–reperfusion

European Journal of Pharmacology ◽

10.1016/j.ejphar.2004.04.048 ◽

2004 ◽

Vol 494 (2-3) ◽

pp. 241-249 ◽

Cited By ~ 30

Author(s):

Gabriela Cavriani ◽

Ricardo Martins Oliveira-Filho ◽

Aryene Góes Trezena ◽

Zilma Lúcia da Silva ◽

Helori Vanni Domingos ◽

...

Keyword(s):

Nitric Oxide ◽

Rat Model ◽

Intestinal Ischemia ◽

Ischemia Reperfusion ◽

Microvascular Permeability ◽

Neutrophil Recruitment ◽

Intestinal Ischemia Reperfusion

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Bradykinin and changes in microvascular permeability in the hamster cheek pouch: role of nitric oxide

British Journal of Pharmacology ◽

10.1111/j.1476-5381.1996.tb15547.x ◽

1996 ◽

Vol 118 (6) ◽

pp. 1371-1376 ◽

Cited By ~ 50

Author(s):

M. Félétou ◽

E. Bonnardel ◽

E. Canet

Keyword(s):

Nitric Oxide ◽

Microvascular Permeability ◽

Cheek Pouch ◽

Hamster Cheek Pouch

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.268.4.r1060 ◽

1995 ◽

Vol 268 (4) ◽

pp. R1060-R1068 ◽

Cited By ~ 6

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.

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Protein kinase C modulates microvascular permeability through nitric oxide synthase

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.271.4.h1702 ◽

1996 ◽

Vol 271 (4) ◽

pp. H1702-H1705 ◽

Cited By ~ 9

Author(s):

M. M. Ramirez ◽

D. D. Kim ◽

W. N. Duran

Keyword(s):

Nitric Oxide ◽

Protein Kinase C ◽

Protein Kinase ◽

Fluorescein Isothiocyanate ◽

Microvascular Permeability ◽

Computer Assisted ◽

Buffer Solution ◽

Bicarbonate Buffer ◽

Macromolecular Transport ◽

Kinase C

Protein kinase C (PKC) serves important functions in signal transduction. We hypothesized that PKC modulation of microvascular permeability to macromolecules is mediated by nitric oxide (NO). To test this hypothesis, we stimulated PKC topically with 10(-7) M phorbol 12,13-dibutyrate (PDBu) in the hamster check pouch microcirculation. NG-monomethyl-L-arginine (L-NMMA) at 10(-4) M was superfused in a bicarbonate buffer solution throughout the experiment to inhibit the activity of NO synthase. We evaluated changes in transport of fluorescein isothiocyanate-labeled 150,000 mol wt dextran by integrated optical intensity (IOI) using intravital fluorometry and computer-assisted digital image analysis. Postcapillary areas were recorded. PDBu increased IOI from baseline to a value of 46.8 +/- 6.3 units (+/- SE). Pretreatment with L-NMMA decreased the PDBu-stimulated increment to 10.8 +/- 0.9 units. These results demonstrate that PKC-activated modulation of macromolecular transport operates through a mechanism involving the production of NO.

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Leukocyte adherence inhibits adenosine-dependent venular control of arteriolar diameter and nitric oxide

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01215.2005 ◽

2006 ◽

Vol 291 (2) ◽

pp. H724-H731 ◽

Cited By ~ 3

Author(s):

Min-ho Kim ◽

Norman R. Harris

Keyword(s):

Nitric Oxide ◽

Adenosine Deaminase ◽

Intravital Microscopy ◽

Leukocyte Adherence ◽

Rat Mesentery ◽

High Adherence ◽

Local Superfusion ◽

Arteriolar Diameter ◽

Adherence Group ◽

Dependent Mechanism

Venular control of arteriolar perfusion has been the focus of several investigations in recent years. This study investigated 1) whether endogenous adenosine helps control venule-dependent arteriolar dilation and 2) whether venular leukocyte adherence limits this response via an oxidant-dependent mechanism in which nitric oxide (NO) levels are decreased. Intravital microscopy was used to assess changes in arteriolar diameters and NO levels in rat mesentery. The average resting diameter of arterioles (27.5 ± 1.0 μm) paired with venules with minimal leukocyte adherence (2.1 ± 0.3 per 100-μm length) was significantly larger than that of unpaired arterioles (24.5 ± 0.8 μm) and arterioles (23.3 ± 1.3 μm) paired with venules with higher leukocyte adherence (9.0 ± 0.5 per 100-μm length). Local superfusion of adenosine deaminase (ADA) induced significant decreases in diameter and perivascular NO concentration in arterioles closely paired to venules with minimal leukocyte adherence. However, ADA had little effect on arterioles closely paired to venules with high leukocyte adherence or on unpaired arterioles. To determine whether the attenuated response to ADA for the high-adherence group was oxidant dependent, the responses were also observed in arterioles treated with 10−4 M Tempol. In the high-adherence group, Tempol fully restored NO levels to those of the low-adherence group; however, the ADA-induced constriction remained attenuated, suggesting a possible role for an oxidant-independent vasoconstrictor released from the inflamed venules. These findings suggest that adenosine- and venule-dependent dilation of paired arterioles may be mediated, in part, by NO and inhibited by venular leukocyte adherence.

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Nitric oxide-induced microvascular permeability alterations: a regulatory role for cGMP

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1993.265.6.h1909 ◽

1993 ◽

Vol 265 (6) ◽

pp. H1909-H1915 ◽

Cited By ~ 6

Author(s):

P. Kubes

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Guanylate Cyclase ◽

Microvascular Permeability ◽

Independent Effect ◽

No Donor ◽

Cyclic Monophosphate ◽

Protein Clearance ◽

Guanylate Cyclase Activation ◽

Permeability Alterations

This study evaluated the physiological effects of compounds that alter guanosine 3',5'-cyclic monophosphate (cGMP) on the increase in vascular protein clearance induced by nitric oxide (NO) synthesis inhibition in the feline small intestine. A lymphatic vessel draining the small bowel was cannulated; vascular protein clearance and intestinal blood flow were measured. N omega-nitro-L-arginine methyl ester (L-NAME), the NO inhibitor, was infused (0.5 mumol/min) into the superior mesenteric artery. Vascular protein clearance increased approximately 4.6-fold, whereas blood flow decreased to 50% of control. Elevation of cGMP by 1) cytosolic guanylate cyclase activation with a NO donor (SIN 1) or 2) a cGMP analogue, 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) completely prevented the rise in microvascular permeability associated with L-NAME. Moreover, these compounds reduced (almost 90%) baseline vascular protein clearance, whereas inhibition of cytosolic guanylate cyclase with methylene blue significantly increased this parameter. Atrial natriuretic factor (ANF) has been reported to increase tissue cGMP levels and microvascular permeability. In this study, ANF did indeed increase intestinal microvascular permeability however this occurred independent of changes in intestinal cGMP levels. These data support a role for cGMP associated with NO-induced microvascular permeability alterations and raise the possibility that ANF has a cGMP-independent effect on microvascular permeability within the intestine.

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