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Removal of endothelial function in coronary resistance vessels by saponin

Summary

Studies of the role of the endothelium in coronary resistance vessels are limited to investigations of endothelium-derived relaxing factor mediated effects using various blocking agents. Endothelium removal as an alternative approach, is restricted to larger epicardial vessels.

This study demonstrates the effect of endothelial damage by saponin on coronary resistance vessels remaining intact within the heart. In an isolated perfused guinea pig heart a saponin-containing solution (50 μg/ml) was infused over 2 min to damage specifically the endothelium. Increases of coronary flow in response to carbachol, histamine, and serotonin were completely blocked and reversed to decreases. Angiotensin-I-induced vasoconstriction was attenuated, whereas angiotensin-II-induced vasoconstriction remained unchanged. Vasodilatory response to sodium-nitroprusside was not attenuated by saponin-treatment. In contrast inhibition of endothelium derived relaxing factor by gossypol inhibited carbachol-induced vasodilation but did not result in vasoconstriction. Electron microscopic examination ensured that while the endothelium was destroyed by saponin-treatment the vascular smooth muscle was left intact. Our data indicate a regulating influence of the vascular endothelium on coronary resistance vessels which can be totally eliminated by saponin-treatment.

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References

  1. Alheid U, Dudel C, Förstermann U (1987) Sclective inhibition by gossypol of endothelium-dependent relaxations augments relaxations to glyceryltrinitrate in rabbit coeliac artery. Br J Pharmacol 92:237–240

    PubMed  Google Scholar 

  2. Chiba S, Tsukada M (1984) Vasoconstrictor responses induced by α-adrenoreceptor agonists before and after removal of the endothelial cells of dog mesenteric arteries. J Auton Pharmac 4:257–260

    Google Scholar 

  3. Chilian WM, Eastham CL, Marcus ML (1986) Microvascular distribution of coronary vascular resistance in beating left ventricle. Am J Physiol 251:H779-H788

    PubMed  Google Scholar 

  4. De Mey JG, Gray SD (1985) Endothelium-dependent reactivity in resistance vessels. Prog appl Microcirc 8:181–187

    Google Scholar 

  5. De Mey JG, Vanhoutte PM (1981) Role of the intima in cholinergic and purinergic relaxation of isolated canine femoral arteries. J Physiol 316:347–355

    PubMed  Google Scholar 

  6. Dezsi L (1987) Suppression of endothelium mediated dilation in coronary resistance vessels by gossypol. Z Kardiol 76(SII):P80

    Google Scholar 

  7. Förstermann U, Goppelt-Struebe M, Frölich JC, Busse R (1986) Inhibitors of acyl-coenzyme A: Lysolecithin acyltransferase activate the production of endothelium-derived vascular relaxing factor. J Pharmac Exp Therap 238:352–359

    Google Scholar 

  8. Förstermann U, Dudel C, Frölich JC (1987) Endothelium-derived relaxing factor is likely to modulate the tone of resistance arteries in rabbit hindlimb in vivo. J Pharmac Exp Therap 243:1055–1061

    Google Scholar 

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

    PubMed  Google Scholar 

  10. Furchgott RF (1984) The role of endothelium in the responses of vascular smooth muscle to drugs. Ann Rev Pharmacol Toxicol 24:175–197

    Google Scholar 

  11. Furchgott RF, Carvalho MH, Kkan MT, Matsunaga K (1987) Evidence for endothelium-dependent vasodilation of resistance vessels by acetylcholine. Blood Vessels 24:145–149

    PubMed  Google Scholar 

  12. Gerlach E, Nees S, Becker BF (1985) The vascular endothelium: a survey of some newly evolving biochemical and physiological features. Basic Res Cardiol 80:459–474

    PubMed  Google Scholar 

  13. Grace GC, Dusting GJ, Kemp BE, Martin TJ (1987) Endothelium and the vasodilator action of rat calcitonin gene-related peptide (cGRP). Br J Pharmacol 91:729–733

    PubMed  Google Scholar 

  14. Griffith TM, Edwards DH, Lewis MJ, Newby AC, Henderson AH (1984a) the nature of endothelium-derived vascular relaxant factor. Nature 308:645–647

    PubMed  Google Scholar 

  15. Griffith TM, Henderson AH, Hughes Edwards D, Lewis MJ (1984b) Isolated perfused rabbit coronary artery and aortic strip preparations: the role of endothelium-derived relaxant factor. J Physiol 351:13–24

    PubMed  Google Scholar 

  16. Hamasaki Y, Tai H (1985) Gossypol, a potent inhibitor of arachidonate 5- and 12-lipoxygenases. Biochim Biophys Acta 834:37–41

    PubMed  Google Scholar 

  17. Hartmann A, Saeed M, Bing RJ (1987) Release of endothelium-derived relaxing factor from freshly harvested porcine endothelial cells. Circ Res 61:548–554

    PubMed  Google Scholar 

  18. Kaiser L, Sparks HV (1987) Endothelial cells—not just a cellophane wrapper. Arch Intern Med 147:569–573

    PubMed  Google Scholar 

  19. Kaley G, Wolin MS, Messina EJ (1986) Endothelium-derived relaxing factors in the microcirculation (abstract). Blood Vessels 23:81

    Google Scholar 

  20. Palmer RMJ, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature (Lond) 327:524–526

    Google Scholar 

  21. Rivers RJ, Duling BR (1986) Are the resistance vessels influenced by an endothelium-derived relaxing factor (EDRF)? Fed Proc 45:196

    Google Scholar 

  22. Rubanyi GM, Lorenz RR, Vanhoutte PM (1985) Bioassay of endothelium-derived relaxing factor(s); inactivation by catecholamines. Am J Physiol 249:H95-H101

    PubMed  Google Scholar 

  23. Saeed M, Schmidli J, Metz M, Bing RJ (1986) Perfused rabbit heart: endothelium-derived relaxing factor in coronary arteries. J Cardiovasc Pharmacol 8:257–261

    PubMed  Google Scholar 

  24. Saye JA, Singer HA, Peach MJ (1984) Role of the endothelium in conversion of angiotensin I to angiotensin II in rabbit aorta. Hypertension 6:216–221

    PubMed  Google Scholar 

  25. Schaper J, Schaper W (1983) Reperfusion in ischemic myocardium: ultrastructural and histochemical aspects. J Am Coll Cardiol 1:1037–1046

    PubMed  Google Scholar 

  26. Stewart DJ, Münzel T, Bassenge E (1987) Reversal of acetylcholine-induced coronary resistance vessel dilation by hemoglobin. European J Pharmacol 136:239–242

    Google Scholar 

  27. Vanhoutte PM, Rubanyi GM, Miller VM, Houston DS (1986) Modulation of vascular smooth muscle contraction by the endothelium. Ann Rev Physiol 48:307–320

    Google Scholar 

  28. Verrecchia C, Sercombe R, Philipson V, Seylaz J (1986) Functional destruction of cerebral vascular endothelium by triton X-100. Blood vessels 23:106

    Google Scholar 

  29. Yamada S, Yamazawa T, Harada Y, Yamamura HI, Nakayama K (1988) Muscarinic receptor subtype in porcine coronary artery. Europ J Pharmacol 150:373–376

    Google Scholar 

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Wiest, E., Trach, V. & Dämmgen, J. Removal of endothelial function in coronary resistance vessels by saponin. Basic Res Cardiol 84, 469–478 (1989). https://doi.org/10.1007/BF01908199

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  • DOI: https://doi.org/10.1007/BF01908199

Key words

  • e ndothelial damage
  • s aponin
  • isolated h eart
  • resistance v essels
  • g ossypol