Abstract
The most prominent pharmacologic effects of the nitrate-nitrite drugs are manifested on the vasculature; the small blood vessels, arterioles, capillaries, and venules. The details of these actions and the response of the cardiovascular system will be considered in this chapter. Other pharmacologic properties include actions on bronchial smooth muscle and cardiovascular enzyme systems.
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References
Anderson, F.F., Craver, B.N.: A pyrex apparatus for the perfusion of the coronary circulation of mammalian hearts. J. Pharmacol. exp. Ther. 93, 135–141 (1948).
Arborelius, M., Lecerof, H., Malm, A., Malmborg, R.O.: Acute effect of nitroglycerin on haemodynamics of angina pectoris. Brit. Heart J. 30, 407–411 (1968).
Aviado, D. M.: The lung circulation. Oxford: Pergamon Press 1965.
Aviado, D.M., Folle, L. E., Bellet, S.: Cardiopulmonary effects of glyceryl trinitrate and isosorbide dinitrate. Cardiologia (Basel) 52, 287–303 (1968 a).
Aviado, D. M., Ito, H., Cho, Y. W., Bellet, S.: Coronary vasodilators on myocardial oxygen consumption and ammonia production. Cardiologia (Basel) 53, 27–46 (1968 b).
Aviado, D.M., Kishimoto, T., Kneidinger, H.J.: Bronchopulmonary effects of pentaerythrityl tetranitrate and isoproterenol. J. Pharmacol. exp. Ther. 165, 274–285 (1969).
Barbour, H.G., Prince, A. L.: The perfused isolated rabbit heart. J. exp. Med. 21, 330–338 (1915).
Barlow, O.W., Beams, A.J.: A comparison of the bronchodilating action of several anti-asthmatic agents after anaphylactic and histamine shock in the guinea pig. J. Pharmacol. exp. Ther. 47, 111–130(1933).
Becker, L.C., Fortuin, N.J., Pitt, B.: Effects of ischemia and antianginal drugs on the distribution of radioactive microspheres in the canine left ventricle. Circulation Res. 28, 263–269 (1971).
Bernstein, L., Friesinger, G.C., Lichtlen, P.R., Ross, R.S.: The effect of nitroglycerin on the systemic and coronary circulation in man and dogs. Circulation 33, 107–116 (1966).
Berry, J. W., Roach, T.C.: An evaluation of blood nitrate levels. Circulation 17, 1014–1046 (1958).
Bing, R. J.: Cardiac metabolism. Physiol. Rev. 45, 171–213 (1965).
Bing, R. J., Bennish, A., Bluemchen, G., Coehen, A., Gallagher, J. P., Zaleski, E. J.: The determination of coronary flow equivalent with coincidence counting technique. Circulation 29, 833–846 (1964).
Bing, R. J., Cowan, C., Bottcher, D., Corsini, G., Daniels, C. G.: A new method of measuring coronary blood flow in man. J. Amer. med. Ass. 205, 277–280 (1968).
Bogaert, M. G.: Organic nitrates in angina pectoris. Arch. int. Pharmacodyn. Ther. 196, 25–34 (1972).
Bogaert, M.G., Rosseel, M.T., DeSchaepdryver, A.F.: The metabolic fate of nitroglycerin (trinitrin) in relation to its vascular effects. Europ. J. Pharmacol. 12, 224–230 (1970).
Brachfeld, N., Bozer, J., Gorlin, R.: Action of nitroglycerin on the coronary circulation in normal and mild cardiac subjects. Circulation 19, 697–704 (1959).
Brandt, J.L., Coccesse, A., Dock, W.: Slitkymographic evidence that nitroglycerine decreases heart volume and stroke volume while increasing amplitude of ballistocardiographic waves. Amer. J. Med. 12, 650–658 (1952).
Bretschneider, H.J., Frank, A., Bernard, I., Kochseik, K., Scheler, F.: Die Wirkung eines Pyrimidopyrimidin-Derivates auf die Sauerstoffversorgung des Herzmuskels. Arzneimittel-Forsch. 9, 49–59 (1959).
Brunton, T.L.: On the use of nitrite of amyl in angina pectoris. Lancet 1867II, 97–98.
Carr, C.J.: The pharmacology of the vasodilator nitrate-nitrite drugs. Int. Rec. Med. 171, 121–129 (1958).
Carr, C.J., Bell, F.K., Bradyhouse, M.F., Krantz, J.C., Jr.: Effect of vasodilators upon the dephosphorylating enzymes of dogs’ coronary arteries. J. Pharmacol. exp. Ther. 108, 385–392 (1953).
Carr, C.J., Burgison, R.M., Fassell, M.S., Krantz, J.C. Jr.: Alkyl nitrites XVI. Comparative depressor responses of octyl nitrite and glyceryl trinitrate. Proc. Soc. exp. Biol. (N.Y.) 76, 759–760(1951).
Otters, R.L., Van: Physiology and biophysics, p.690. Theodore C. Ruch and Harry D. Patton, (Eds.). Philadelphia, Pa: W. B. Saunders Co. 1966.
Cohen, A., Gallagher, J.P., Luebs, E.D., Varga, Z., Yamanaka, J., Zaleski, E.J., Bluemchen, C., Bing, R.J.: The quantitative determination of coronary flow with a positron emitter (rubidium 84). Circulation 32, 636–649 (1965).
Cuny, L., Quivy, D.: Action vaso-dilatatrice de la trinitrine, etudieé par la Plethysmographie de la muqueuse nasale. C.R. Soc. Biol. (Paris) 136, 283–284 (1942).
Darby, T.D., Aldinger, E.E.: Further studies of the effect on myocardial energy utilization elicited by nitroglycerin. Circulation Res. 8, 100–108 (1960).
Davidson, I.W.F., Miller, H.S., DiCarlo, F.J.: Absorption, excretion and metabolism of pentaerythritol tetranitrate by humans. J. Pharmacol. exp. Ther. 175, 42–50 (1970).
Davidson, I.W.F., Miller, H.S., DiCarlo, F.J.: Pharmacodynamics and biotransformation of pentaerythritol tetranitrate in man. J. Pharm. Sci. 60, 274–277 (1971).
DeMaria, A.N., Vismara, L.A., Auditore, K., Amsterdam, E.A., Zelis, R., Mason, D.T.: Effects of nitroglycerin on left ventricular cavity size and cardiac performance determined by ultrasound in man. Amer. Soc. Clin. Pharmacol. Ther. 1974 meeting abstract. Clin. Pharmacol. Ther. 15, 204(1974).
DiCarlo, F.J., Coutinko, C.B., Crew, M.C.: Sites of absorption of pentaerythritol tetranitrate. Arch. Int. Pharmacodyn. Ther. 167, 163–170 (1967).
Domenech, R.J., Hoffman, J.I.E., Noble, M.I.M., Saunders, K.B., Henson, J.R., SubijAnto, S.: Total and regional coronary blood flow measured by radioactive microspheres in consicious and anesthetized dogs. Circulation Res. 25, 581–596 (1969).
Dresdale, D.T., Yuceoglu, Y.Z., Reyes, A., Jr., Lunger, M., Nassar, A.M.: Hemodynamic effects of isosorbide dinitrate in patients with rheumatic heart disease and pulmonary hypertension. A preliminary study. Angiology 14, 349–357 (1963).
Eckenhoff, J.E., Hafkenschiel, J.H.: Effect of nikethamide on coronary blood flow and cardiac oxygen metabolism. J. Pharmacol. exp. Ther. 91, 362–369 (1947).
Eckenhoff, J.E., Hafkenschiel, J.H., Harmel, M.H., Goodale, W.T., Lubin, M., Bing, R.J., Kety, S. S.: Measurement of coronary blood flow by the nitrous oxide method. Amer. J. Physiol. 152, 356–364 (1948).
Eckstein, R.W., Newberry, W.B., McEachen, J.A., Smith, G.: Studies of the anti-adrenergic effects of nitroglycerin on the dog heart. Circulation 4, 534–540 (1951).
Essex, H.E., Herrick, J.F., Baldes, E.J., Mann, F.C.: Blood flow in the circumflex branch of the left coronary artery of the intact dog. Amer. J. Physiol. 117, 271–279 (1936).
Fam, W.M., McGregor, M.: Effect of nitroglycerin and dipyridamole on regional coronary resistance. Circulation Res. 22, 649–659 (1968).
Ferrer, M. I., Bradley, S.E., Wheeler, H.O., Enson, Y., Preisig, R., Bricker, P.W., Conroy, R.J., Harvey, R.M.: Some effects of nitroglycerin upon the splanchnic pulmonary, and systemic circulations. Circulation 33, 357–373 (1966).
Fortuin, N.J., Kaihara, S., Becker, L.C., Pitt, B.: Regional myocardial blood flow in the dog studied with radioactive microspheres. Cardiovasc. Res. 5, 331–336 (1971).
Fremont, R.E.: The actions of organic nitrates on the cardiopulmonary and peripheral circulations. Angiology 12, 391–400 (1961).
Gillis, R.A., Melville, ICI.: Coronary flow changes and cardiac adrenergic blockade during nitroglycerin infusions. Europ. J. Pharmacol. 13, 15–22 (1970).
Goldstein, R. E., Stinson, E.B., Epstein, S. E.: Effects of nitroglycerin on coronary collateral function in patients with coronary occlusive disease. Abstracts. Amer. J. Cardiol. 31, 135 (1973).
Gorlin, R., Brachfeld, N., MacLeod, C., Bopp, P.: Effect of nitroglycerin on the coronary circulation in patients with coronary artery disease or increased left ventricular work. Circulation 19, 705–718(1959).
Gregg, D.E.: The coronary circulation in health and disease. Philadelphia, Pa.: Lea and Febiger 1950.
Gregg, D.E., Longino, F.H., Green, P.A., Czerwonka, L.J.: A comparison of coronary flow determination of the nitrous oxide method and by a direct method using the rotameter. Circulation 3, 89–94 (1951).
Haddy, F.J.: Physiology and pharmacology of the coronary circulation and myocardium, particularly in relation to coronary artery disease. Amer. J. Med. 47, 274–286 (1969).
Hirshleifer, I., Arora, Y.: Nitrites in the treatment of bronchial asthma. Dis. Chest 36, 275–283 (1961).
Hollander, W., Madoff, I.M., Chobanian, A.V.: Local myocardial blood flow as indicated by the disappearance of NaI131 from the heart muscle: Studies at rest, during exercise, and following nitrite administration. J. Pharmacol. exp. Ther. 139, 53–59 (1963).
Johnson, J.B., Fairley, A., Carter, C.: Effects of sublingual nitroglycerin on pulmonary arterial pressure in patients with left ventricular failure. Ann. intern. Med. 50, 34–42 (1959).
Johnson, J.B., Gross, J.F., Hale, E.: Effects of sublingual administration of nitroglycerin on pulmonary-artery pressure in patients with failure of the left ventricule. New Engl. J. Med. 257, 1114–1117(1957).
Kaihara, S., VanHeerden, P.D., Migita, T., Wagner, H.N.: Measurement of distribution of cardiac output. J. Appl. Physiol. 25, 696–700 (1968).
Khouri, E.M., Gregg, D.E.: Minature electromagnetic flow meter applicable to coronary arteries. J. Appl. Physiol. 18, 224–227 (1963).
Kolin, A.: (1960) Circulatory system. Methods; blood flow determination by electromagnetic method. In: Glasser, O. (Ed.): Medical Physics, Vol. III, pp.141–155. Chicago, Ill.: Year Book Publ. Inc. 1960.
Kolin, A.: Cardiovascular research. VI. World Congress of Cardiology, London Sept. 1970.
Krantz, J.C., Jr., Carr, C.J., Bryant, H.H.: Alkyl nitrites. XIV. The effect of nitrites and nitrates on arterial triphosphatase. J. Pharmacol. exp. Ther. 102, 16–21 (1951).
Krantz, J.C., Jr., Carr, C.J., Forman, S.E.: The pharmacology of 2-ethylhexyl nitrite. J. Pharmacol. exp. Ther. 64, 302–306 (1938).
Krantz, J.C., Jr., Carr, C.J., Forman, S.E.: Alkyl nitrites. V. The pharmacology of the high molecular weight alkyl nitrites. Proc. Soc. exp. Biol. (N.Y.) 42, 472–474 (1939 a).
Krantz, J.C., Jr., Carr, C.J., Forman, S.E., Ellis, F.W.: Alkyl nitrates. III. A pharmacologic study of a new series of organic nitrates. J. Pharmacol. exp. Ther. 67, 187–190 (1939 b).
Krantz, J.C., Jr., Lu, G.G., Bell, F. K., Cascorbi, H.F.: Nitrites. XIX. Studies of the mechanism of action of glyceryl trinitrate. Biochem. Pharmacol. 11, 1095–1099 (1962).
Langendorff, O.: Pflügers Arch. ges. Physiol. 61, 291 (1895). Cited by Charlier, 1971.
Leighninger, D.S., Rueger, R., Beck, C.S.: Effect of glyceryl trinitrate (nitroglycerin) on arterial blood supply to ischemic myocardium. Amer. J. Cardiol. 3, 638–646 (1959).
Levy, J. V.: Effect of organic nitrates on myocardial oxygen consumption in vitro. Brit. J. Pharmacol. 38, 743–748 (1970).
Mason, D.T., Zelis, R., Amsterdam, E.A.: Actions of the nitrites on the peripheral circulation and myocardial oxygen consumption: significance in the relief of angina pectoris. Dis. Chest 59, 296–305(1971).
Melville, K.I., Gillis, R.A., Sekelj, P.: Coronary flow, blood pressure and heart dose-response changes after nitroglycerin administration. Canad. J. Physiol. Pharmacol. 43, 9–18 (1965).
Morawitz, P., Zahn, K.: Dtsch. Arch. klin. Med. 116, 364–370 (1914). Cited by Krantz et al. (1939 a).
Muller, O., Rorvik, K.: Hemodynamic consequences of coronary heart disease. Brit. Heart J. 20, 302–310(1958).
Murrell, W.: Nitro-glycerine as a remedy for angina pectoris. Lancet 1879I, 80–81, 113–115, 151–152,225–227.
Needleman, P., Hunter, F. E., Jr.: The transformation of glyceryl trinitrate and other nitrates by glutathione-organic nitrate reductase. Mol. Pharmacol. 1, 77–86 (1965).
Parker, J.O., Ledwick, J.R., West, R.O., Case, R.B.: Reversible cardiac failure during angina pectoris. Circulation 39, 745–757 (1969).
Parker, J.O., West, F.R.O., Giorgi, S.: The effect of nitroglycerin on coronary blood flow and the hemodynamic response to exercise in coronary artery disease. Amer. J. Cardiol. 27, 59–65(1971).
Popovich, N.R., Roberts, F.F., Crislip, R.L., Menges, H., Jr.: Ineffectiveness of nitroglycerine as an antiadrenergic agent on the cat heart. Circulation Res. 4, 727–730 (1956).
Rath, M., Krantz, J.C., Jr.: Nitrites. VIII. Blood-nitrite content of man and other species. J. Pharmacol. exp. Ther. 76, 27–32 (1942a).
Rath, M., Krantz, J.C., Jr.: Nitrites. IX. A further study of the action of organic nitrates. J. Pharmacol. exp. Ther. 76, 33–38 (1942b).
Ritschel, W.A., Clotten, R.: Entwicklung einer peroralen nitroglycerinprophyllin-retard-form. Arzneimittel-Forsch. 20, 1180–1187 (1970).
Robinson, B.F.: Mode of action of nitroglycerin in angina pectoris. Brit. Heart J. 30, 295–302 (1968).
Ross, R.S., Ueda, K., Lichtlen, P.R., Rees, J.R.: Measurement of myocardial blood flow in animals and man by selective injection of radioactive gas into the coronary arteries. Circulation Res. 15, 28–41 (1964).
Rosseel, M.T., Bogaert, M.G.: Gas chromatography of the nitrate esters of glycerol, isosorbide and isomannide. J. Chromatog. 65, 364–367 (1972).
Roughgarden, J.W., Newman, E.V.: Circulatory changes during the pain of angina pectoris. Amer. J. Med. 41, 935–945 (1966).
Rowe, G.G.: The nitrous oxide method for determining coronary flow in man. Amer. Heart J. 58, 268–281(1959).
Rowe, G.G.: Effects of drugs on the coronary circulation of man. Clin. Pharmacol. Ther. 7, 547–557 (1966).
Rowe, G.G., Castillo, C.A., Afonso, S., Crumpton, C.W.: Coronary flow measured by the nitrous oxide method. Amer. Heart J. 67, 457–468 (1964).
Rowe, G.G., Chelius, C. J., Alfonso, S., Gurtner, H.P., Crumpton, C.W.: Systemic and coronary hemodynamic effects of erythrol tetranitrate. J. clin. Invest. 40, 1217–1222 (1961).
Scheline, R.R.: Metabolism of foreign compounds by gastrointestinal microorganisms. Pharmacol. Rev. 25, 451–523 (1973).
Sevelius, G., Johnson, P.C.: Myocardial blood flow determined by surface counting and ratio formula. J. Lab. clin. Med. 54, 669–679 (1959).
Stieglitz, E.J., Palmer, A.E.: A colormetric method for the determination of nitrite in blood. J. Pharmacol. exp. Ther. 51, 398–410 (1934).
Stieglitz, E.J., Palmer, A.E.: Nitrite in normal human blood. Arch. intern. Med. 59, 620–624 (1937).
Tawab, S.A., Carr, C.J., Krantz, C.J.: The pharmacology of thiocyanobenzoic acids. J. Pharmacol. exp. Ther. 96, 416–421 (1949).
Taylor, S.H.: Reversible left-ventricular failure in angina pectoris. Lancet 31, 902–907 (1970).
Truitt, E.B., Jr.: A note on the modification of the Anderson-Craver perfusion apparatus for interchanging perfusion fluids. J. Amer. Pharm. Ass. 44, 382 (1955).
Voegtlin, C., Macht, D.I.: The action of nitrites and drugs on the digitalis group on the isolated coronary artery. J. Pharmacol. exp. Ther. 5, 77–86 (1913).
Vyden, J.K., Carvalho, M., Boszormenyi, E.: Effect of glyceryl trinitrate (nitroglycerin) on the systemic and coronary circulation of the dog. Amer. J. Cardiol. 25, 53–58 (1970).
West, J. W., Guzman, S.V.: Coronary dilation and constriction visualized by selective arteriography. Circulation Res. 7, 527–536 (1959).
Whitworth, C.G., Grant, M.M.: Use of nitrate and nitrite vasodilators by glaucomatous patients. Arch. Ophthal. 71, 492–496 (1964).
Williams, J.F., Glick, G., Brunwald, W.: Studies on cardiac dimensions in intact anesthesized man. Circulation 32, 767–771 (1965).
Winbury, M. M.: Experimental approaches to the development of antianginal drugs. Advanc. Pharmacol. 3, 1–82 (1964).
Winbury, M.M.: Problems in laboratory evaluation of antianginal agents, p.26. Amsterdam: North Holland Pub. Co. 1967.
Winbury, M. M.: Redistribution of left ventricular blood flow produced by nitroglycerin. Circulation Res. Suppl. No. 1.1, 140–147 (1971).
Winbury, M.M., Gobel, L.P.: Effect of nitrites on nutritional circulation of heart and hindlimb. Amer. J. Physiol. 212, 1062–1066 (1967).
Winbury, M.M., Hawe, B.B., Weiss, H.R.: Effect of nitroglycerine and dipyridamole on epicardial and endocardial oxygen tension — further evidence for redistributc of myocardial blood flow. J. Pharmacol. exp. Ther. 176, 184–199 (1971).
Zobell, C.E.: Factors influencing the reduction of nitrates and nitrites by bacteria in semisolid media. J. Bacteriol. 24, 273–281 (1932).
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Carr, C.J. (1975). Pharmacological Properties. In: Needleman, P. (eds) Organic Nitrates. Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology, vol 40. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-66024-5_4
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