Abstract
Calcium ions (Ca2+) play an important role in excitation-contraction coupling in muscle (including vascular smooth muscle) and also in excitation-secretion coupling in neurons and endocrine cells. Endothelium-dependent relaxation of blood vessels in response to numerous pharmacological [e.g., acetylcholine, adenosine diphosphate (ADP), and so on] and physiological (e.g., increase in flow) stimuli is mediated by a still-unidentified substance (“endothelium-derived relaxing factor” or EDRF; Furchgott, 1983) released from endothelial cells (Furchgott, 1983; Peach et al., 1985; Vanhoutte et al., 1986). The sequence of events leading to endothelium-dependent relaxation is initiated by an excitation-secretion coupling mechanism in endothelial cells leading to the release of endothelium-derived relaxing factor, resembling events occurring in neurons (initiating the release of neurotransmitters) or in endocrine cells (initiating the release of a hormone). That Ca2+ plays an important role in the release of endothelium-derived relaxing factor from endothelial cells was indicated by the finding that the Ca2+ ionophore A23187 evokes endothelium-dependent relaxation in a variety of blood vessels isolated from different species (for ref., see Furchgott, 1983) and stimulates the release of endothelium-derived relaxing factor from perfused rabbit aorta (Griffith et al., 1984) and cultured endothelial cells (Cocks et al., 1985).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Cocks, T. M., Angus, J. A., Campbell, J. H., and Campbell, G. R.: Release and properties of endothelium-derived relaxing factor (EDRF) from endothelial cells in culture. J. Cell Physiol 123:310–320, 1985.
De Mey, J. G. and Vanhoutte, P. M.: Interaction between Na+, K+ exchanges and the direct inhibitory effect of acetylcholine on canine femoral arteries. Circ. Res. 46:826–836, 1980.
Deth, R. and Van Breemen, C.: Relative contributions of Ca2+-influx and cellular Ca2+ released during drug-induced activation of the rabbit aorta. Pflugers. Arch. Gen. Physiol. 348:13–22, 1974.
Dube, G. P., Baik, Y. H., Vaghy, P. L., and Schwartz, A.: Nitrendipine potentiates Bay K 8644-induced contraction of isolated porcine coronary artery: Evidence for functionally distinct dihydropyridine receptor subtypes. Biochem. Biophys. Res. Comm. 128:1295–1302, 1985.
Furchgott, R. F.: Role of the endothelium in responses of vascular smooth muscle. Circ. Res. 53:557–573, 1983.
Furchgott, R. F., Zawadzki, J. V., and Cherry, P. D.: Role of Endothelium in the Vasodilator Response to Acetylcholine, in Vasodilatation (Vanhoutte, P. M. and Leusen, I., eds.) Raven, New York, 1981.
Gordon, J. L. and Martin, W.: Endothelium-dependent relaxation of the pig aorta: Relationship to stimulation of 86Rb efflux from isolated endothelial cells. Br. J. Pharmacol 79:531–541, 1983.
Griffith, T., Edwards, D., Lewis, M., Newby, A., and Henderson, A.: The nature of endothelium-derived relaxing factor. Nature 308:645–647, 1984.
Griffith, T. M., Edwards, D. H., Newby, A. C., Lewis, M. J., and Henderson, A. H.: Production of endothelium-derived relaxing factor is dependent on oxidative phosphorylation and extracellular calcium. Cardiovas. Res. 20:7–12, 1986.
Hof, R. P., Ruegg, U. T., Hof, A., and Vogel, A.: Stereoselectivity at the calcium channel; opposite action of the enantiomers of a 1,4-dihydropyridine. J. Cardiovasc. Pharmacol. 7:689, 1985.
Holzmann, S.: Endothelium-induced relaxation by acetylcholine associated with larger rises in cyclic GMP in coronary arterial strips. J. Cyclic Nucleotide Res. 8:409–419, 1982.
Jurkowitz, M. S., Altschuld, R. A., Brierley, G. P., and Crague, E. L., Jr.: Inhibition of Na+-dependent Ca2+ efflux from heart mitochondria by amiloride analogues. Fed. Eur. Biochem. Soc. 162:262–265, 1983.
Loeb, A. L., Johns, R. A., and Peach, M. J.: Phospholipase activation by melittin releases prostacyclin and an endothelium-derived relaxing factor from rabbit aorta. Blood Vessels 23:86, 1986.
Long, C. J. and Stone, T. W.: The release of endothelium-derived relaxing factor is calcium dependent. Blood Vessels 22:205–208, 1985.
Luckhoff, A. and Busse, R.: Increased free calcium in endothelial cells under stimulation with adenine nucleotides. J. Cell. Physiol. 126:414–420, 1986.
Matlib, M. A., Lee, S. W., Depover, A., and Schwartz, A.: A specific inhibitory action of certain benzothiazepines and benzodiazepines on the sodium-calcium exchange process of heart and brain mitochondria. Eur. J. Pharmacol. 89:327–328, 1983.
Miller, R. C., Schoeffter, P., and Stoclet, J. C: Insensitivity of calcium-dependent endothelium stimulation in rat isolated aorta to the calcium entry blocker, flunarizine. Br. J. Pharmacol. 85:481–487, 1985.
Nilius, B., Hess, P., Lansman, J. B., and Tsien, R. W.: A novel type of cardiac channel in ventricular cells. Nature 316:443–446, 1985.
Nowycky, M. C., Fox, A. P., and Tsien, R. W.: Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature 316:440–443, 1985.
Peach, M. J., Loeb, A. L., Singer, H. A., and Saye, J. A.: Endothelium-derived vascular relaxing factor. Hypertension 7 (suppl. I):I94–I100, 1985.
Rapoport, R. M. and Murad, F.: Agonist-induced endothelium-dependent relaxation in rat thoracic aorta may be mediated through cGMP. Circ. Res. 52:352–357, 1983.
Rubanyi, G. M., Schwartz, A., and Vanhoutte, P. M.: The calcium agonists Bay K 8644 and (+)202,791 stimulate the release of endothelium relaxing factor from canine femoral arteries. Eur. J. Pharmacol. 117:143–144, 1985a.
Rubanyi, G. M., Schwartz, A., and Vanhoutte, P. M.: The effect of diltiazem and verapamil on endothelium-dependent responses in canine blood vessels. Pharmacologist 27:290, 1985.
Rubanyi, G. M., Schwartz, A., and Vanhoutte, P. M.: Calcium-channel agonists stimulate the release of endothelial relaxing factor from perfused canine femoral arteries. FASEB, St. Louis, Missouri, 1986.
Schoeffler, P. and Miller, R. C: Role of sodium-calcium exchange and effects of calcium entry blockers on endothelial-mediated responses in rat isolated aorta. Mol. Pharmacol. 30:53–57, 1986.
Schramm, M., Thomas, G., Towart, R., and Franchowiak, G.: Novel dihydropyridine with positive inotropic action through activation of Ca++ channels. Nature 303:535–537, 1983.
Siegl, P. K. S., Cragoe, E. J., Jr., Trumble, M. J., and Kaczorowski, G. J.: Inhibition of Na+/Ca2+ exchange in membrane vesicle and papillary muscle preparations from guinea pig heart by analogs of amiloride. Proc. Natl. Acad. Sci. USA 81:3238–3242, 1984.
Singer, H. A. and Peach, M. J.: Calcium- and endothelial-mediated vascular smooth muscle relaxation in rabbit aorta. Hypertension 4 (suppl. II): 19–25, 1982.
Spedding, M., Schini, V., Schoeffter, P., and Miller, R. C: Calcium channel activation does not increase release of endothelium-derived relaxing factors (EDRF) in rat aorta although tonic release of EDRF may modulate calcium channel activity in the smooth musccle. J. Cardiovasc. Pharmacol. 8:1130–1137, 1986.
Vaghy, P. L., Johnson, J. D., Matlib, M. A., Wang, T., and Schwartz, A.: Selective inhibition of Na+-induced Ca2+ release from heart mitochondria by diltiazem and certain other Ca2+ antagonist drugs. J. Biol. Chem. 257:6000, 1982.
Van Breemen, C., Aaronson, P., and Loutzenhiser, R.: Sodium-calcium interactions in mammalian smooth muscle. Pharmacol. Rev. 30:167–208, 1979.
Vanhoutte, P. M., Rubanyi, G. M., Miller, V. M., and Houston, D. S.: Modulation of vascular smooth muscle contraction by the endothelium. Ann. Rev. Physiol. 48:307–320, 1986.
Williams, J. S., Baik, Y. H., and Schwartz, A.: Interactions between calcium agonists and antagonists in coronary smooth muscle: Role of the endothelium. Blood Vessels 23:No. 2, abstract, 1986.
Winquist, R. J., Bunting, P. B., and Schofield, T. L.: Blockade of endothelium-dependent relaxation by the amiloride analog dichlorobenzamil: Possible role of Na+/Ca++ exchange in the release of endothelium-derived relaxing factor. J. Pharmacol. Exp. Ther. 235:644–650, 1985.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1988 The Humana Press Inc.
About this chapter
Cite this chapter
Rubanyi, G.M., Schwartz, A., Vanhoutte, P.M. (1988). Calcium Transport Mechanisms in Endothelial Cells Regulating the Synthesis and Release of Endothelium-Derived Relaxing Factor. In: Vanhoutte, P.M. (eds) Relaxing and Contracting Factors. The Endothelium. Humana Press. https://doi.org/10.1007/978-1-4612-4588-9_9
Download citation
DOI: https://doi.org/10.1007/978-1-4612-4588-9_9
Publisher Name: Humana Press
Print ISBN: 978-1-4612-8939-5
Online ISBN: 978-1-4612-4588-9
eBook Packages: Springer Book Archive