Abstract
The goal of this study was to determine the role of the synthesis and release of nitric oxide in modulating alterations in microvascular permeability of the hamster cheek pouch in response to adenosine 5′-diphosphate and bradykinin. We used intravital fluorescent microscopy to examine the permeability of the hamster cheek pouch to agonists before and following application of enzymatic inhibitors of nitric oxide, NG-monomethyl-l-arginine (l-NMMA; 0.01, 0.1, and 1.0 μM) and Nw-nitro-l-arginine methyl ester (l-NAME; 0.01, 0.1, and 1.0 μM). Increases in permeability of the hamster cheek pouch were quantitated by the formation of microvascular leaky sites. ADP and bradykinin produced an increase in the number of venular leaky sites, and superfusion ofl-NMMA andl-NAME significantly decreased ADPand bradykinin-induced increases in microvascular permeability. To determine the specificity of nitric oxide blockade on microvascular permeability, we examined changes in permeability in response to adenosine, and examined the effects ofd-NMMA on microvascular permeability. Adenosine-induced increases in permeability were not altered by treatment withl-NMMA, andd-NMMA did not inhibit ADP-induced increases in microvascular permeability. Thus, these findings suggest that production of nitric oxide, in response to application of ADP and bradykinin, has a role in modulating macromolecular permeability of the hamster cheek pouch in vivo.
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References
Vanhoutte, P. M. 1988. Platelets, endothelium and blood vessel wall.Experientia 44:105–109.
Furchgott, R. F., andP. M. Vanhoutte. 1989. Endothelium-derived relaxing and contracting factors.FASEB J. 3:2007–2018.
Vanhoutte, P. M., andD. S. Houston. 1985. Platelets, endothelium, and vasospasm.Circulation 72:728–734.
Houston, D. S., J. T. Shepherd, andP. M. Vanhoutte. 1985. Adenine nucleotides, serotonin, and endothelium dependent relaxations to platelets.Am. J. Physiol. 248:H389-H395.
Rivers, R. J., A. L. Loeb, N. J. Izzo, M. J. Peach, andB. R. Duling. 1990. Microcirculatory responses to exogenous endothelial cell-derived relaxing factor.Am. J. Physiol. 258:H606-H609.
Rees, D. D., R. M. J. Palmer, H. F. Hodson, andS. Moncada. 1989. A specific inhibitor of nitric oxide formation froml-arginine attenuates endothelium-dependent relaxation.Br. J. Pharmacol. 96:418–424.
Palmer, R. M. J., A. G. Ferrige, andS. Moncada. 1987. Nitric oxide release accounts for the biological activity of endothelium derived relaxing factor.Nature 327:524–528.
Ignarro, L. J. 1990. Biosynthesis and metabolism of endothelium-derived nitric oxide.Annu. Rev. Pharmacol. Toxicol. 30:535–560.
Mayhan, W. G., andW. L. Joyner. 1984. The effect of altering the external calcium concentration and a calcium channel blocker, verapamil, on microvascular leaky sites and dextran clearance in the hamster cheek pouch.Microvasc. Res. 28:159–179.
Mayhan, W. G., G. Sahagun, R. Spector, andD. D. Heistad. 1986. Effects of leukotriene C4 on the cerebral microvasculature.Am. J. Physiol. 251:H471-H474.
Murray, M. A., D. D. Heistad, andW. G. Mayhan. 1991. Role of protein kinase C in bradykinin-induced increases in microvascular permeability.Circ. Res. 68:1340–1348.
Yong, T., andW. G. Mayhan. 1992. Effect of prostaglanin E1 on leukotriene C4-induced increases in vascular permeability of hamster cheek pouch.Inflammation 16:159–167.
Svensjo, E., andW. L. Joyner. 1984. The effects of intermittent and continuous stimulation of microvessels in the cheek pouch of hamsters with histamine and bradykinin on the development of venular leaky sites.Microcirc. Endothel. Lymph. 1:381–396.
Svensjo, E. 1978. Characterization of leakage of macromolecules in postcapillary venules.Acta Univ. Ups. 34:1–42.
Svensjo, E., K. E. Arfors, R. M. Raymond, andG. J. Grega. 1979. Morphological and physiological correlation of bradykinin-induced macromolecular efflux.Am. J. Physiol. 236:H600-H606.
Svensjo, E. 1978. Bradykinin and prostaglandin E1, E2, and F2α induced macromolecular leakage in the hamster cheek pouch.Prostagland. Med. 1:397–410.
Mitchell, J. A., G. De Nucci, T. D. Warner, andJ. R. Vane. 1991. Alkaline buffers release EDRF from bovine cultured aortic endothelial cells.Br. J. Pharmacol. 103:1295–1302.
Gawlowski, D. M., andW. N. Duran. 1986. Dose related effects of adenosine and bradykinin on microvascular permselectivity to macromolecules in the hamster cheek pouch.Circ. Res. 58:348–355.
Hughes, S. R., T. J. Williams, andS. D. Brain. 1990. Evidence that endogenous nitric oxide modulates oedema formation induced by substance P.Eur. J. Pharmacol. 191:481–484.
Palmer, R. M. J., D. S. Ashton, andS. Moncada. 1988. Vascular endothelial cells synthesize nitric oxide froml-arginine.Nature 333:664–666.
Masini, E., D. Salvemini, A. Pistelli, P. F. Mannaioni, andJ. R. Vane. 1991. Rat mast cells synthesize a nitric oxide like-factor which modulates the release of histamine.Agents Actions 33:61–63.
Collier, J., andP. Vallance. 1991. Physiological importance of nitric oxide.Br. Med. J. 302:1289–1290.
Moncada, S., R. M. J. Palmer, andE. A. Higgs. 1991. Nitric oxide: Physiology, pathophysiology and pharmacology.Pharmacol. Rev. 43:109–142.
Majno, G., andG. E. Palade. 1961. Studies on inflammation I. The effect of histamine and serotonin on vascular permeability: An electron microscopic study.J. Biophys. Biochem. Cytol. 11:571–605.
Majno, G., S. M. Shea, andM. Leventhal. 1969. Endothelial contraction produced by histamine-type mediators.J. Cell Biol. 42:647–672.
Hulstrom, D., andE. Svensjo. 1979. Intravital and electron microscopy study of bradykinininduced vascular permeability changes using FITC-dextran as a tracer.J. Pathol. 129:125–133.
Shasby, D. M., S. S. Shasby, J. M. Sullivan, andM. J. Peach. 1982. Role of endothelial cell cytoskeleton in control of endothelial permeability.Circ. Res. 51:657–661.
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Mayhan, W.G. Role of nitric oxide in modulating permeability of hamster cheek pouch in response to adenosine 5′-diphosphate and bradykinin. Inflammation 16, 295–305 (1992). https://doi.org/10.1007/BF00917622
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DOI: https://doi.org/10.1007/BF00917622