| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CARDIOVASCULAR |
1 Program in Vascular Biology, Department of Pharmacology & Physiology and Department of Surgery, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School, Newark, NJ 07101- 1709, USA
2 Department of Physiological Sciences, Pontifical Catholic University of Chile, Santiago, Chile
3 Department of Pharmacology, Yale University School of Medicine, New Haven, 06510-0812, CT, USA
Nitric oxide (NO) is an important regulator of blood flow, but its role in permeability is still challenged. We tested in vivo the hypotheses that: (a) endothelial nitric oxide synthase (eNOS) is not essential for regulation of baseline permeability; (b) eNOS is essential for hyperpermeability responses in inflammation; and (c) molecular inhibition of eNOS with caveolin-1 scaffolding domain (AP-Cav) reduces eNOS-regulated hyperpermeability. We used eNOS-deficient (eNOS–/–) mice and their wild-type control as experimental animals, platelet-activating factor (PAF) at 10–7 M as the test pro-inflammatory agent, and integrated optical intensity (IOI) as an index of microvascular permeability. PAF increased permeability in wild-type cremaster muscle from a baseline of 2.4 ± 2.2 to a peak net value of 84.4 ± 2.7 units, while the corresponding values in cremaster muscle of eNOS–/– mice were 1.0 ± 0.3 and 15.6 ± 7.7 units (P < 0.05). Similarly, PAF increased IOI in the mesentery of wild-type mice but much less in the mesentery of eNOS–/– mice. PAF increased IOI to comparable values in the mesenteries of wild-type mice and those lacking the gene for inducible NOS (iNOS). Administration of AP-Cav blocked the microvascular hyperpermeability responses to 10–7 M PAF. We conclude that: (1) baseline permeability does not depend on eNOS; (2) eNOS and NO are integral elements of the signalling pathway for the hyperpermeability response to PAF; (3) iNOS does not affect either baseline permeability or hyperpermeability responses to PAF; and (4) caveolin-1 inhibits eNOS regulation of microvascular permeability in vivo. Our results establish eNOS as an important regulator of microvascular permeability in inflammation.
(Received 21 February 2006;
accepted after revision 1 May 2006;
first published online 4 May 2006)
Corresponding author W. N. Durán: Department of Pharmacology & Physiology, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School, 185 South Orange Ave, MSB H-638, PO Box 1709, Newark, NJ 07101-1709, USA. Email: duran{at}umdnj.edu
This article has been cited by other articles:
|
|
 |
|
  F. A. Sanchez, D. D. Kim, R. G. Duran, C. J. Meininger, and W. N. Duran Internalization of eNOS via caveolae regulates PAF-induced inflammatory hyperpermeability to macromolecules Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1642 - H1648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Furst, M. F. Bubik, P. Bihari, B. A. Mayer, A. G. Khandoga, F. Hoffmann, M. Rehberg, F. Krombach, S. Zahler, and A. M. Vollmar Atrial Natriuretic Peptide Protects against Histamine-Induced Endothelial Barrier Dysfunction in Vivo Mol. Pharmacol., July 1, 2008; 74(1): 1 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. D. Bauser-Heaton, J. Song, and H. G. Bohlen Cerebral microvascular nNOS responds to lowered oxygen tension through a bumetanide-sensitive cotransporter and sodium-calcium exchanger Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2166 - H2173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Reichel, M. Rehberg, P. Bihari, C. M. Moser, S. Linder, A. Khandoga, and F. Krombach Gelatinases mediate neutrophil recruitment in vivo: evidence for stimulus specificity and a critical role in collagen IV remodeling J. Leukoc. Biol., April 1, 2008; 83(4): 864 - 874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Viita, J. Markkanen, E. Eriksson, M. Nurminen, K. Kinnunen, M. Babu, T. Heikura, S. Turpeinen, S. Laidinen, T. Takalo, et al. 15-Lipoxygenase-1 Prevents Vascular Endothelial Growth Factor A- and Placental Growth Factor-Induced Angiogenic Effects in Rabbit Skeletal Muscles via Reduction in Growth Factor mRNA Levels, NO Bioactivity, and Downregulation of VEGF Receptor 2 Expression Circ. Res., February 1, 2008; 102(2): 177 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Surapisitchat, K.-I. Jeon, C. Yan, and J. A. Beavo Differential Regulation of Endothelial Cell Permeability by cGMP via Phosphodiesterases 2 and 3 Circ. Res., October 12, 2007; 101(8): 811 - 818. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
