Pflügers Archiv

, Volume 422, Issue 6, pp 564–569 | Cite as

Arterial size determines the enhancement of contractile responses after suppression of endothelium-derived relaxing factor formation

  • Jan Galle
  • Johann Bauersachs
  • Eberhard Bassenge
  • Rudi Busse
Heart, Circulation, Respiration and Blood; Environmental and Exercise Physiology


We studied the effect of endothelium-derived relaxing factor (EDRF) on norepinephrine-induced contractile responses and on the tissue guanosine-3′,5′-phosphate (cGMP) concentration of isolated rabbit arteries with an increasing endothelium to smooth muscle cell ratio (aorta, femoral and mesenteric arteries). After suppression of EDRF formation (either by NG-nitro-l-arginine or, in mesenteric arteries, by saponin), contractions elicited by cumulative doses of norepinephrine were unaltered in aorta but were enhanced by 22.5% in femoral arteries and by 44.3% in mesenteric arteries (at the highest norepinephrine concentration). The cGMP concentration (pmol/mg protein) of unstimulated, endotheliumintact vessels decreased after suppression of EDRF formation from 1.09±0.24 to 0.74±0.28 in aortic, from 2.86±0.4 to 0.61±0.19 in femoral and from 6.3±0.9 to 0.7±0.15 in mesenteric arterial segments. The basal cGMP concentration did not differ in endothelium-denuded segments of these arteries, suggesting a similar basal activity of soluble guanylate cyclase (sGC). A higher sensitivity of sGC may have contributed to the higher cGMP concentration observed in the smaller arteries, since in the presence of sodium nitroprusside the cGMP concentration of endothelium-denuded segments increased 1.8-fold in aortic, 2.9-fold in femoral and 2.4 fold in mesenteric arterial segments. However, these differences in sGC activation cannot be solely responsible for the high basal cGMP concentration in endotheliumintact mesenteric arteries. The greater ratio of endothelium to smooth muscle cell layers in the smaller arteries might result in a higher EDRF concentration in the vascular wall and subsequently in a higher cGMP concentration. In conclusion, these data support the view of a greater importance of EDRF-mediated vascular control in small arteries than in large conduit arteries.

Key words

Vascular reactivity Endothelium Smooth muscle cells cGMP NG-nitro-l-arginine Endothelium-derived relaxing factor (EDRF) Nitric oxide 


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  1. 1.
    Arnold WP, Mittal CK, Katsuki S, Murad F (1977) Nitric oxide activates guanylate cyclase and increases guanosine 3′,5′cyclic monophosphate levels in various tissue preparations. Proc Natl Acad Sci USA 74:3203–3207Google Scholar
  2. 2.
    Busse R, Pohl U, Kellner C, Klemm U (1983) Endothelial cells are involved in the vasodilatory response to hypoxia. Pflügers Arch 397:78–80Google Scholar
  3. 3.
    Chen G, Yamamoto Y, Miwa K, Suzuki H (1991) Hyperpolarization of arterial smooth muscle induced by endothelial humoral substances. Am J Physiol 260:H1888-H1892Google Scholar
  4. 4.
    Chiba S, Tsukada M (1984) Potentiation of KCl-induced vasoconstriction by saponin treatment in isolated canine mesenteric arteries. Jpn J Pharmacol 36:535–537Google Scholar
  5. 5.
    Chu A, Chambers DE, Lin CC, Kuehl WD, Cobb FR (1990) Nitric oxide modulates epicardial coronary basal vasomotor tone in awake dogs. Am J Physiol 258:H1250-H1254Google Scholar
  6. 6.
    Chu, A, Chambers DE, Lin CC, Kuehl WD, Palmer RMJ, Moncada S, Cobb FR (1991) Effects of inhibition of nitric oxide formation on basal vasomotion and endothelium-dependent responses of the coronary arteries in awake dogs. J Clin Invest 87:1964–1968Google Scholar
  7. 7.
    Collins P, Chappell SP, Griffith TM, Lewis MJ, Henderson AH (1986) Differences in basal endothelium-derived relaxing factor activity in different artery types. J Cardiovasc Pharmacol 8:1158–1162Google Scholar
  8. 8.
    Feletou M, Vanhoutte PM (1988) Endothelium-dependent hyperpolarization of canine coronary smooth muscle. Br J Pharmacol 93:515–524Google Scholar
  9. 9.
    Förstermann U, Hertting G, Neufang B (1986) The role of endothelial and non-endothelial prostaglandins in the relaxation of isolated blood vessels of the rabbit induced by acetylcholine and bradykinin. Br J Pharmacol 87:521–532Google Scholar
  10. 10.
    Förstermann U, Mülsch A, Böhme E, Busse R (1986) Stimulation of soluble guanylate cyclase by an acetylcholine-induced endothelium-derived factor from rabbit and canine arteries. Circ Res 58:531–538Google Scholar
  11. 11.
    Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376Google Scholar
  12. 12.
    Ignarro LJ (1989) Biological actions and properties of endothelium-derived nitric oxide formed and released from artery and vein. Circ Res 65:1–21Google Scholar
  13. 13.
    Ignarro LJ, Byrns RE, Wood KS (1987) Endothelium-dependent modulation of cGMP levels and intrinsic smooth muscle tone in isolated bovine intrapulmonary artery and vein. Circ Res 60:82–92Google Scholar
  14. 14.
    Jackson WF, Mülsch A, Busse R (1991) Rhythmic smooth muscle activity in hamster aortas is mediated by continuous release of NO from the endothelium. Am J Physiol 260:H248-H253Google Scholar
  15. 15.
    Kelm M, Schrader J (1990) Control of coronary vascular tone by nitric oxide. Circ Res 66:1561–1575Google Scholar
  16. 16.
    Lamontagne D, Pohl U, Busse R (1992) Mechanical deformation of vessel wall and shear stress determine the basal EDRF release in the intact coronary vascular bed. Circ Res 70:123–130Google Scholar
  17. 17.
    Liu SF, Crawley DE, Evans TW, Barnes PJ (1991) Endogenous nitric oxide modulates adrenergic neural vasoconstriction in guinea-pig pulmonary artery. Br J Pharmacol 104:565–569Google Scholar
  18. 18.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  19. 19.
    Myers RR, Minor RL, Guerra R, Bates JN, Harrison DG (1990) Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrocysteine than nitric oxide. Nature 365:161–163Google Scholar
  20. 20.
    Nagao T, Vanhoutte PM (1991) Membrane hyperpolarization contributes to endothelium-dependent relaxations induced by acetylcholine in the femoral vein of the rat. Am J Physiol 261:H1034-H1037Google Scholar
  21. 21.
    Palmer RMJ, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526Google Scholar
  22. 22.
    Pohl U, Busse R (1989) EDRF increases cyclic GMP in platelets during passage through the coronary vascular bed. Circ Res 65:1798–1803Google Scholar
  23. 23.
    Pohl U, Holtz J, Busse R, Bassenge E (1986) Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension 8:37–44Google Scholar
  24. 24.
    Schoeffter P, Lugnier C, Demesy-Waeldele F, Stoclet JC (1987) Role of cyclic AMPand cyclic GMP-phosphodiesterases in the control of cyclic nucleotide levels and smooth muscle tone in rat isolated aorta. Biochem Pharmacol 36:3965–3972Google Scholar
  25. 25.
    Taylor S, Weston A (1988) Endothelium-derived hyperpolarizing factor: a new endogenous inhibitor from the vascular endothelium. Trends Pharmacol Sci 9:72–74Google Scholar
  26. 26.
    Wolin MS, Rodenburg JM, Messina EJ, Kaley G (1990) Similarities in the pharmacological modulation of reactive hyperemia and vasodilation to H2O2 in rat skeletal muscle arterioles: Effects of probes for endothelium-derived mediators. J Pharmacol Exp Ther 253:508–512Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Jan Galle
    • 1
  • Johann Bauersachs
    • 2
  • Eberhard Bassenge
    • 2
  • Rudi Busse
    • 2
  1. 1.Department of Medicine IVUniversity of FreiburgFreiburgGermany
  2. 2.Department of Applied PhysiologyUniversity of FreiburgFreiburgGermany

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