Skip to main content
PMC home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1995 Sep;4(5):344–349. doi: 10.1155/S096293519500055X

Rate of perfusion modulates colloidal carbon leakage from rat intestinal microvessels in vitro

A M Northover 1,✉, B J Northover 1
PMCID: PMC2365652  PMID: 18475662

Abstract

In order to investigate the effects of varying the rate of flow on endothelial integrity the rat isolated small intestinal vasculature was perfused at 1, 5, 10 or 20 ml/min with a gelatin-containing physiological salt solution (GPSS), followed by an injection of colloidal carbon suspension (CC). Significantly greater microvascular CC leakage occurred at 1 or 5 ml/min than at 10 or 20 ml/ mitt. CC leakage at the two slower rates of flow was reduced by adding red blood cells to the GPSS, suggesting that the microvascular endothelium became hypoxic when perfused with GPSS at 1 or 5 ml/min. After perfusion at 20 ml/min with GPSS containing resiniferatoxin (1 μM) or 5-hydroxytryptamine (100 μM), CC leakage was significantly lower than after similar perfusion at 10 ml/min. Two nitric oxide (NO) synthesis blockers, N-nitro-L-arginine methyl ester (L-NAME, 100 μM) and methylene blue (20 μM), and an NO scavenger CPTIO (100 μM) each increased CC leakage. This suggests that NO was being produced at perfusion rates of 10 or 20 ml/min. Sodium nitroprusside (10 μM), 8-bromo-cGMP (100 μM) and BN52021 (10 μM) each significantly reduced CC leakage in the presence of L-NAME.

Full Text

The Full Text of this article is available as a PDF (585.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akaike T., Yoshida M., Miyamoto Y., Sato K., Kohno M., Sasamoto K., Miyazaki K., Ueda S., Maeda H. Antagonistic action of imidazolineoxyl N-oxides against endothelium-derived relaxing factor/.NO through a radical reaction. Biochemistry. 1993 Jan 26;32(3):827–832. doi: 10.1021/bi00054a013. [DOI] [PubMed] [Google Scholar]
  2. Filep J. G., Földes-Filep E. Modulation by nitric oxide of platelet-activating factor-induced albumin extravasation in the conscious rat. Br J Pharmacol. 1993 Dec;110(4):1347–1352. doi: 10.1111/j.1476-5381.1993.tb13967.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Frangos J. A., Eskin S. G., McIntire L. V., Ives C. L. Flow effects on prostacyclin production by cultured human endothelial cells. Science. 1985 Mar 22;227(4693):1477–1479. doi: 10.1126/science.3883488. [DOI] [PubMed] [Google Scholar]
  4. Fujii E., Irie K., Uchida Y., Tsukahara F., Muraki T. Possible role of nitric oxide in 5-hydroxytryptamine-induced increase in vascular permeability in mouse skin. Naunyn Schmiedebergs Arch Pharmacol. 1994 Oct;350(4):361–364. doi: 10.1007/BF00178952. [DOI] [PubMed] [Google Scholar]
  5. Gertler J. P., Ocasio V. H. Endothelin production by hypoxic human endothelium. J Vasc Surg. 1993 Aug;18(2):178–184. [PubMed] [Google Scholar]
  6. Grabowski E. F., Jaffe E. A., Weksler B. B. Prostacyclin production by cultured endothelial cell monolayers exposed to step increases in shear stress. J Lab Clin Med. 1985 Jan;105(1):36–43. [PubMed] [Google Scholar]
  7. Gruetter C. A., Barry B. K., McNamara D. B., Gruetter D. Y., Kadowitz P. J., Ignarro L. Relaxation of bovine coronary artery and activation of coronary arterial guanylate cyclase by nitric oxide, nitroprusside and a carcinogenic nitrosoamine. J Cyclic Nucleotide Res. 1979;5(3):211–224. [PubMed] [Google Scholar]
  8. Hasséssian H., Bodin P., Burnstock G. Blockade by glibenclamide of the flow-evoked endothelial release of ATP that contributes to vasodilatation in the pulmonary vascular bed of the rat. Br J Pharmacol. 1993 Jun;109(2):466–472. doi: 10.1111/j.1476-5381.1993.tb13592.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kourembanas S., McQuillan L. P., Leung G. K., Faller D. V. Nitric oxide regulates the expression of vasoconstrictors and growth factors by vascular endothelium under both normoxia and hypoxia. J Clin Invest. 1993 Jul;92(1):99–104. doi: 10.1172/JCI116604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kuchan M. J., Jo H., Frangos J. A. Role of G proteins in shear stress-mediated nitric oxide production by endothelial cells. Am J Physiol. 1994 Sep;267(3 Pt 1):C753–C758. doi: 10.1152/ajpcell.1994.267.3.C753. [DOI] [PubMed] [Google Scholar]
  11. Kurose I., Fukumura D., Miura S., Sekizuka E., Nagata H., Suematsu M., Tsuchiya M. Nitric oxide mediates vasoactive effects of endothelin-3 on rat mesenteric microvascular beds in vivo. Angiology. 1993 Jun;44(6):483–490. doi: 10.1177/000331979304400609. [DOI] [PubMed] [Google Scholar]
  12. Lincoln T. M. Effects of nitroprusside and 8-bromo-cyclic GMP on the contractile activity of the rat aorta. J Pharmacol Exp Ther. 1983 Jan;224(1):100–107. [PubMed] [Google Scholar]
  13. László F., Whittle B. J., Moncada S. Interactions of constitutive nitric oxide with PAF and thromboxane on rat intestinal vascular integrity in acute endotoxaemia. Br J Pharmacol. 1994 Dec;113(4):1131–1136. doi: 10.1111/j.1476-5381.1994.tb17114.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Majno G., Shea S. M., Leventhal M. Endothelial contraction induced by histamine-type mediators: an electron microscopic study. J Cell Biol. 1969 Sep;42(3):647–672. doi: 10.1083/jcb.42.3.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Martin W., Villani G. M., Jothianandan D., Furchgott R. F. Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta. J Pharmacol Exp Ther. 1985 Mar;232(3):708–716. [PubMed] [Google Scholar]
  16. Mayhan W. G. Nitric oxide accounts for histamine-induced increases in macromolecular extravasation. Am J Physiol. 1994 Jun;266(6 Pt 2):H2369–H2373. doi: 10.1152/ajpheart.1994.266.6.H2369. [DOI] [PubMed] [Google Scholar]
  17. Mittal C. K., Arnold W. P., Murad F. Characterization of protein inhibitors of guanylate cyclase activation from rat heart and bovine lung. J Biol Chem. 1978 Feb 25;253(4):1266–1271. [PubMed] [Google Scholar]
  18. Northover A. M. An in vitro method for assessing the effects of pro-inflammatory and anti-inflammatory compounds on microvascular permeability in the rat small intestine. J Pharmacol Toxicol Methods. 1993 Aug;29(4):227–232. doi: 10.1016/1056-8719(93)90030-i. [DOI] [PubMed] [Google Scholar]
  19. Northover A. M., Northover B. J. Involvement of protein kinase C in the control of microvascular permeability to colloidal carbon. Agents Actions. 1993 Jul;39(3-4):132–136. doi: 10.1007/BF01998965. [DOI] [PubMed] [Google Scholar]
  20. Northover A. M., Northover B. J. Lectin-induced increase in microvascular permeability to colloidal carbon in vitro may involve protein kinase C activation. Agents Actions. 1994 May;41(3-4):136–139. doi: 10.1007/BF02001906. [DOI] [PubMed] [Google Scholar]
  21. Northover A. M., Northover B. J. Possible bi-directional link between ET(A) receptors and protein kinase C in rat blood vessels. Mediators Inflamm. 1995;4(1):55–59. doi: 10.1155/S096293519500010X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Northover A. M., Northover B. J. Stimulation of protein kinase C activity may increase microvascular permeability to colloidal carbon via alpha-isoenzyme. Inflammation. 1994 Oct;18(5):481–487. doi: 10.1007/BF01560695. [DOI] [PubMed] [Google Scholar]
  23. Pohl U., Holtz J., Busse R., Bassenge E. Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension. 1986 Jan;8(1):37–44. doi: 10.1161/01.hyp.8.1.37. [DOI] [PubMed] [Google Scholar]
  24. Rapoport R. M., Murad F. Endothelium-dependent and nitrovasodilator-induced relaxation of vascular smooth muscle: role of cyclic GMP. J Cyclic Nucleotide Protein Phosphor Res. 1983;9(4-5):281–296. [PubMed] [Google Scholar]
  25. Rubanyi G. M., Vanhoutte P. M. Hypoxia releases a vasoconstrictor substance from the canine vascular endothelium. J Physiol. 1985 Jul;364:45–56. doi: 10.1113/jphysiol.1985.sp015728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wanstall J. C., Hughes I. E., O'Donnell S. R. Evidence that nitric oxide from the endothelium attenuates inherent tone in isolated pulmonary arteries from rats with hypoxic pulmonary hypertension. Br J Pharmacol. 1995 Jan;114(1):109–114. doi: 10.1111/j.1476-5381.1995.tb14913.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES