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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 May;118(2):228–232. doi: 10.1111/j.1476-5381.1996.tb15391.x

Endogenous inotropic factor-induced endothelium-dependent relaxation of vascular smooth muscle.

C Han 1, J C Khatter 1
PMCID: PMC1909640  PMID: 8735619

Abstract

1. Possible contractile or relaxation effects of an endogenous inotropic factor (EIF) isolated and purified from porcine heart left ventricle were examined in rat isolated aortic ring preparations. 2. EIF induced a dose-dependent relaxation of the rat isolated aortic ring preparation pre-contracted with 0.4 microM phenylephrine (PE); 200 microliters (in 5 ml bath) of EIF caused relaxation of aortic rings by as much as 67.4 +/- 4.5%. In another set of experiments, in the presence of 100 microliters EIF, the PE concentration-response contractile curve shifted to the right, the maximal contractile force was reduced by as much as 32.8% and the EC50 of PE increased from 0.2 to 0.3 microM. 3. The relaxation effect of EIF was demonstrated to be endothelium-dependent. Additional experiments demonstrated that EIF-induced relaxation in an isolated aortic ring could be inhibited by 2 microM NG-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, suggesting the involvement of nitric oxide in EIF-induced relaxation of the muscle. 4. Atropine (0.2 microM) or indomethacin (10 microM) had no significant effect on EIF-induced relaxation. 5. These data suggest that EIF, a novel endogenous inotrope from porcine myocardium, also acts as an endothelium-dependent vasodilator substance mediating relaxation in the rat isolated aorta mainly by release of nitric oxide. The possibility of EIF acting through muscarinic receptor and the involvement of prostacyclin were excluded.

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Selected References

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  1. Agbanyo M., Khatter J. C. Purification and characterization of endogenous digitalis-like substance (DLS) from pig heart. Res Commun Chem Pathol Pharmacol. 1990 Apr;68(1):41–54. [PubMed] [Google Scholar]
  2. Angus J. A., Cocks T. M. Endothelium-derived relaxing factor. Pharmacol Ther. 1989;41(1-2):303–352. doi: 10.1016/0163-7258(89)90112-5. [DOI] [PubMed] [Google Scholar]
  3. Balzan S., Ghione S., Clerico A., Montali U. Correlation between endogenous digoxin-like immunoreactivity and 3H-ouabain displacement on erythrocyte membranes in extracts of human plasma. Clin Biochem. 1986 Oct;19(5):311–314. doi: 10.1016/s0009-9120(86)80048-0. [DOI] [PubMed] [Google Scholar]
  4. Chen Q. M., Chau T., Agbanyo M., Navaratnam S., Khatter J. C., Bose D. Pharmacological characterization of the activity of endogenous inotropic factor from porcine left ventricle. J Cardiovasc Pharmacol. 1993;22 (Suppl 2):S93–S95. doi: 10.1097/00005344-199322002-00030. [DOI] [PubMed] [Google Scholar]
  5. Crawley D. E., Liu S. F., Evans T. W., Barnes P. J. Inhibitory role of endothelium-derived relaxing factor in rat and human pulmonary arteries. Br J Pharmacol. 1990 Sep;101(1):166–170. doi: 10.1111/j.1476-5381.1990.tb12107.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ebara H., Suzuki S., Nagashima K., Koizumi T., Nishida A., Kanbe Y., Kuroume T. Digoxin- and digitoxin-like immunoreactive substances in amniotic fluid, cord blood, and serum of neonates. Pediatr Res. 1986 Jan;20(1):28–31. doi: 10.1203/00006450-198601000-00007. [DOI] [PubMed] [Google Scholar]
  7. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  8. Goto A., Yamada K., Yagi N., Hui C., Nagoshi H., Sasabe M., Yoshioka M. Digitalis-like factors from human urine. J Cardiovasc Pharmacol. 1993;22 (Suppl 2):S58–S59. doi: 10.1097/00005344-199322002-00019. [DOI] [PubMed] [Google Scholar]
  9. Gruber K. A., Whitaker J. M., Buckalew V. M., Jr Endogenous digitalis-like substance in plasma of volume-expanded dogs. Nature. 1980 Oct 23;287(5784):743–745. doi: 10.1038/287743a0. [DOI] [PubMed] [Google Scholar]
  10. Haddy F. J. Endogenous digitalis-like factor or factors. N Engl J Med. 1987 Mar 5;316(10):621–623. doi: 10.1056/NEJM198703053161010. [DOI] [PubMed] [Google Scholar]
  11. Haddy F. J., Pamnani M. B. The role of a humoral sodium-potassium pump inhibitor in low-renin hypertension. Fed Proc. 1983 Jul;42(10):2673–2680. [PubMed] [Google Scholar]
  12. Hallaq H. A., Haupert G. T., Jr Positive inotropic effects of the endogenous Na+/K(+)-transporting ATPase inhibitor from the hypothalamus. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10080–10084. doi: 10.1073/pnas.86.24.10080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hamlyn J. M., Blaustein M. P., Bova S., DuCharme D. W., Harris D. W., Mandel F., Mathews W. R., Ludens J. H. Identification and characterization of a ouabain-like compound from human plasma. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6259–6263. doi: 10.1073/pnas.88.14.6259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Huang H. C., Lee C. R., Weng Y. I., Lee M. C., Lee Y. T. Vasodilator effect of scoparone (6,7-dimethoxycoumarin) from a Chinese herb. Eur J Pharmacol. 1992 Jul 21;218(1):123–128. doi: 10.1016/0014-2999(92)90155-w. [DOI] [PubMed] [Google Scholar]
  15. Kelly R. A., O'Hara D. S., Canessa M. L., Mitch W. E., Smith T. W. Characterization of digitalis-like factors in human plasma. Interactions with NaK-ATPase and cross-reactivity with cardiac glycoside-specific antibodies. J Biol Chem. 1985 Sep 25;260(21):11396–11405. [PubMed] [Google Scholar]
  16. Khatter J. C., Agbanyo M., Hoeschen R. J. Endogenous digitalis-like substance in pig left ventricle. Life Sci. 1986 Dec 22;39(25):2483–2492. doi: 10.1016/0024-3205(86)90491-1. [DOI] [PubMed] [Google Scholar]
  17. Khatter J. C., Agbanyo M., Navaratnam S. Endogenous inotropic substance from heart tissue has digitalis-like properties. Life Sci. 1991;48(5):387–396. doi: 10.1016/0024-3205(91)90493-u. [DOI] [PubMed] [Google Scholar]
  18. Knowles R. G., Moncada S. Nitric oxide as a signal in blood vessels. Trends Biochem Sci. 1992 Oct;17(10):399–402. doi: 10.1016/0968-0004(92)90008-w. [DOI] [PubMed] [Google Scholar]
  19. Moncada S., Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993 Dec 30;329(27):2002–2012. doi: 10.1056/NEJM199312303292706. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Navaratnam S., Chau T., Agbanyo M., Bose D., Khatter J. C. Positive inotropic effect of porcine left ventricular extract on canine ventricular muscle. Br J Pharmacol. 1990 Oct;101(2):370–374. doi: 10.1111/j.1476-5381.1990.tb12716.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Palmer R. M., Rees D. D., Ashton D. S., Moncada S. L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun. 1988 Jun 30;153(3):1251–1256. doi: 10.1016/s0006-291x(88)81362-7. [DOI] [PubMed] [Google Scholar]
  23. Park W. K., Lynch C., 3rd, Johns R. A. Effects of propofol and thiopental in isolated rat aorta and pulmonary artery. Anesthesiology. 1992 Nov;77(5):956–963. doi: 10.1097/00000542-199211000-00019. [DOI] [PubMed] [Google Scholar]
  24. Rees D. D., Palmer R. M., Schulz R., Hodson H. F., Moncada S. Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol. 1990 Nov;101(3):746–752. doi: 10.1111/j.1476-5381.1990.tb14151.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wang Y. X., Poon C. I., Pang C. C. Vascular pharmacodynamics of NG-nitro-L-arginine methyl ester in vitro and in vivo. J Pharmacol Exp Ther. 1993 Dec;267(3):1091–1099. [PubMed] [Google Scholar]

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