Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Apr;108(4):1107–1110. doi: 10.1111/j.1476-5381.1993.tb13512.x

Porcine ventricular endocardial cells in culture express the inducible form of nitric oxide synthase.

J A Smith 1, M W Radomski 1, R Schulz 1, S Moncada 1, M J Lewis 1
PMCID: PMC1908162  PMID: 7683563

Abstract

1. We have investigated whether porcine endocardial cells in culture express the inducible, Ca(2+)-independent form of nitric oxide (NO) synthase. 2. NO synthase activity in cytosolic extracts of endocardial cells was measured by estimation of the rate of formation of L-[14C]-citrulline from L-[14C]-arginine. 3. Treatment of the cells in culture with lipopolysaccharide or cytokines induced a Ca(2+)-independent NO synthase activity in the cell cytosol. The combination of tumour necrosis factor (TNF alpha, 10 ng ml-1) and interleukin-1 beta (IL-1 beta, 10 ng ml-1) induced the greatest enzyme activity. 4. The increased Ca(2+)-independent NO synthase activity following exposure to cytokines was paralleled by an increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels in the endocardial cell cytosol. 5. Simultaneous addition of dexamethasone (0.01-1 microM) or cycloheximide (0.03-3 microM) inhibited in a concentration-dependent manner TNF alpha- and IL-1 beta-induced expression of Ca(2+)-independent NO synthase activity. Neither dexamethasone (1 microM) nor cycloheximide (3 microM) had any effect on the activity of the constitutive NO synthase. 6. The possible pathophysiological consequences of endocardial expression of the inducible NO synthase are discussed.

Full text

PDF
1107

Selected References

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

  1. Busse R., Mülsch A. Induction of nitric oxide synthase by cytokines in vascular smooth muscle cells. FEBS Lett. 1990 Nov 26;275(1-2):87–90. doi: 10.1016/0014-5793(90)81445-t. [DOI] [PubMed] [Google Scholar]
  2. Girolami J. P., Bascands J. L., Pécher C., Berlan M., Montastruc J. L., Montastruc P. Yohimbine increases submaxillary kallikrein release into the saliva in dogs: evidence for alpha 2-adrenoceptor-mediated inhibition of cholinergic pathways. Br J Pharmacol. 1991 Feb;102(2):351–354. doi: 10.1111/j.1476-5381.1991.tb12177.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gross S. S., Jaffe E. A., Levi R., Kilbourn R. G. Cytokine-activated endothelial cells express an isotype of nitric oxide synthase which is tetrahydrobiopterin-dependent, calmodulin-independent and inhibited by arginine analogs with a rank-order of potency characteristic of activated macrophages. Biochem Biophys Res Commun. 1991 Aug 15;178(3):823–829. doi: 10.1016/0006-291x(91)90965-a. [DOI] [PubMed] [Google Scholar]
  4. Henderson A. H. St Cyres lecture. Endothelium in control. Br Heart J. 1991 Mar;65(3):116–125. doi: 10.1136/hrt.65.3.116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Kilbourn R. G., Belloni P. Endothelial cell production of nitrogen oxides in response to interferon gamma in combination with tumor necrosis factor, interleukin-1, or endotoxin. J Natl Cancer Inst. 1990 May 2;82(9):772–776. doi: 10.1093/jnci/82.9.772. [DOI] [PubMed] [Google Scholar]
  6. Lewis M. J., Shah A. M., Smith J. A., Henderson A. H. Does endocardium modulate myocardial contractile performance? Cardioscience. 1990 Jun;1(2):83–87. [PubMed] [Google Scholar]
  7. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  8. Radomski M. W., Palmer R. M., Moncada S. Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells. Proc Natl Acad Sci U S A. 1990 Dec;87(24):10043–10047. doi: 10.1073/pnas.87.24.10043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Rees D. D., Cellek S., Palmer R. M., Moncada S. Dexamethasone prevents the induction by endotoxin of a nitric oxide synthase and the associated effects on vascular tone: an insight into endotoxin shock. Biochem Biophys Res Commun. 1990 Dec 14;173(2):541–547. doi: 10.1016/s0006-291x(05)80068-3. [DOI] [PubMed] [Google Scholar]
  10. Salter M., Knowles R. G., Moncada S. Widespread tissue distribution, species distribution and changes in activity of Ca(2+)-dependent and Ca(2+)-independent nitric oxide synthases. FEBS Lett. 1991 Oct 7;291(1):145–149. doi: 10.1016/0014-5793(91)81123-p. [DOI] [PubMed] [Google Scholar]
  11. Schulz R., Nava E., Moncada S. Induction and potential biological relevance of a Ca(2+)-independent nitric oxide synthase in the myocardium. Br J Pharmacol. 1992 Mar;105(3):575–580. doi: 10.1111/j.1476-5381.1992.tb09021.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Schulz R., Smith J. A., Lewis M. J., Moncada S. Nitric oxide synthase in cultured endocardial cells of the pig. Br J Pharmacol. 1991 Sep;104(1):21–24. doi: 10.1111/j.1476-5381.1991.tb12378.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Shah A. M., Lewis M. J., Henderson A. H. Effects of 8-bromo-cyclic GMP on contraction and on inotropic response of ferret cardiac muscle. J Mol Cell Cardiol. 1991 Jan;23(1):55–64. doi: 10.1016/0022-2828(91)90038-n. [DOI] [PubMed] [Google Scholar]
  14. Smith J. A., Shah A. M., Lewis M. J. Factors released from endocardium of the ferret and pig modulate myocardial contraction. J Physiol. 1991 Aug;439:1–14. doi: 10.1113/jphysiol.1991.sp018653. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES