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The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine


Despite its very potent vasodilating action in vivo, acetylcholine (ACh) does not always produce relaxation of isolated preparations of blood vessels in vitro. For example, in the helical strip of the rabbit descending thoracic aorta, the only reported response to ACh has been graded contractions, occurring at concentrations above 0.1 µM and mediated by muscarinic receptors1,2. Recently, we observed that in a ring preparation from the rabbit thoracic aorta, ACh produced marked relaxation at concentrations lower than those required to produce contraction3,4 (confirming an earlier report by Jelliffe5). In investigating this apparent discrepancy, we discovered that the loss of retaxation by ACh in the case of the strip was the result of unintentional rubbing of its intimai surface against foreign surfaces during its preparation. If care was taken to avoid rubbing of the intimai surface during preparation, the tissue, whether ring, transverse strip or helical strip, always exhibited relaxation to ACh, and the possibility was considered that rubbing of the intimai surface had removed endothelial cells4. We demonstrate here that relaxation of isolated preparations of rabbit thoracic aorta and other blood vessels by ACh requires the presence of endothelial cells, and that ACh, acting on muscarinic receptors of these cells, stimulates release of a substance(s) that causes relaxation of the vascular smooth muscle. We propose that this may be one of the principal mechanisms for ACh-induced vasodilation in vitio. Preliminary reports on some aspects of the work have been reported elsewhere4,6.

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  1. 1

    Furchgott, R. F. Pharmac. Rev. 7, 183–265 (1955).

    CAS  Google Scholar 

  2. 2

    Furchgott, R. F. & Bhadrakom, S. J. Pharmac. exp. Ther. 108, 129–143 (1953).

    CAS  Google Scholar 

  3. 3

    Furchgott, R. F., Davidson, D. & Lin, C. I. Blood Vessels 16, 213 (1979).

    Google Scholar 

  4. 4

    Furchgott, R. F. & Zawadzki, J. V. Pharmacologist 21, 271 (1979).

    Google Scholar 

  5. 5

    Jelliffe, R. W. J. Pharmac. exp. Ther. 135, 349–353 (1962).

    CAS  Google Scholar 

  6. 6

    Furchgott, R. F. & Zawadzki, J. V. Fedn Proc. 39, 581 (1980).

    Google Scholar 

  7. 7

    Furchgott, R. F., Ehrreich, S. J. & Greenblatt, E. J. gen. Physiol. 44, 499–519 (1961).

    CAS  Article  Google Scholar 

  8. 8

    Poole, J. C. F., Sanders, A. G. & Florey, H. W. J. Path. Bact. 75, 133–143 (1958).

    CAS  Article  Google Scholar 

  9. 9

    Jaffe, E. A., Nachman, R. L., Becker, C. G. & Minick, C. R. J. clin. Invest. 52, 2745–2756 (1973).

    CAS  Article  Google Scholar 

  10. 10

    DeMey, J. G. & Vanhoutte, P. M. Archs int. Pharmacodyn. Thér. 234, 339 (1978).

    CAS  Google Scholar 

  11. 11

    Flower, R. J. Pharmac. Rev. 26, 33–67 (1974).

    CAS  Google Scholar 

  12. 12

    Flower, R. J. & Blackwell, G. C. Biochem. Pharmac. 25, 285–291 (1976).

    CAS  Article  Google Scholar 

  13. 13

    Higgs, G. A. et al. Abstr. 7th int. Congr. Pharmac., 334 (Pergamon, Oxford, 1978).

    Google Scholar 

  14. 14

    Rand, M. J. & Varma, B. Br. J. Pharmac. 38, 758–770 (1970).

    CAS  Article  Google Scholar 

  15. 15

    Hume, W. R., DeLalande, I. S. & Waterson, J. G. Eur. J. Pharmac. 17, 227–233 (1972).

    CAS  Article  Google Scholar 

  16. 16

    Steinsland, O. S., Furchgott, R. F. & Kirpekar, S. M. J. Pharmac. exp. Ther. 184, 346–356 (1973).

    CAS  Google Scholar 

  17. 17

    Vanhoutte, P. M. Circulation Res. 34, 317–326 (1974).

    CAS  Article  Google Scholar 

  18. 18

    Löffelholz, K. & Muscholl, E. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 265, 1–15 (1969).

    Article  Google Scholar 

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Furchgott, R., Zawadzki, J. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288, 373–376 (1980).

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