Little is known about how the vascular reactivity of the coronary microcirculation is affected by upstream atherosclerotic disease. We have examined, with a wire myograph, the responses of intramyocardial arteries from hearts in which the epicardial vessels were either free of atherosclerotic lesions (non-diseased group) or were affected by atherosclerosis (diseased group). Vasodilator responses of preconstricted vessels to substance P (84.1 ± 12.6 compared to 42.0 ± 19.7%) were less in vessels from the diseased group (p < 0.05). In contrast, the relaxation to bradykinin (70.2 ± 21.2 compared to 100.6 ± 7.9%) was increased in vessels from the diseased group (p < 0.05). The dilator responses to acetylcholine, adenosine diphosphate, histamine and sodium nitroprusside showed no significant differences between arteries from each group. 5-Hydroxytryptamine was without any significant vasodilator effect in arteries from either group. Assessment of contractile function revealed that the responses to 5-hydroxytryptamine, acetylcholine, U46619, endothelin-1 and L-NG-monomethylarginine in each group were not significantly different. Histamine, noradrenaline and dopamine were without any significant contractile response. These results demonstrate that upstream atherosclerosis does not confer any global impairment of endothelium-dependent vasorelaxant responses or smooth muscle hyperreactivity to vasoconstrictors in the arteries that penetrate the myocardium.

1.
Bossaller C, Habib GB, Yamamoto H, Williams C, Wells S, Henry PD: Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5′-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta. J Clin Invest 1987;79:170–174.
2.
Heistad DD, Armstrong ML, Marcus ML, Piegors DJ, Mark AL: Augmented responses to vasoconstrictor stimuli in hypercholesterolemic and atherosclerotic monkeys. Circ Res 1984;54:711–718.
3.
Henry PD, Yokoyama M: Supersensitivity of atherosclerotic rabbit aorta to ergonovine. Mediation by a serotonergic mechanism. J Clin Invest 1980;66:306–313.
4.
McLenachan JM, Vita J, Fish DR, Treasure CB, Cox DA, Ganz P, Selwyn AP: Early evidence of endothelial vasodilator dysfunction at coronary branch points. Circulation 1990;82:1169–1173.
5.
Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, Ganz P: Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 1986;315:1046–1051.
6.
Chester AH, O’Neil GS, Moncada S, Tadjkarimi S, Yacoub MH: Low basal and stimulated release of nitric oxide in atherosclerotic epicardial coronary arteries. Lancet 1990;336:897–900.
7.
Chester AH, Martin GR, Bodelsson M, Arneklo Nobin B, Tadjkarimi S, Tornebrandt K, Yacoub MH: 5-Hydroxytryptamine receptor profile in healthy and diseased human epicardial coronary arteries. Cardiovasc Res 1990;24:932–937.
8.
Berkenboom G, Unger P, Fontaine J: Atherosclerosis and responses of human isolated coronary arteries to endothelium-dependent and -independent vasodilators. J Cardiovasc Pharmacol 1989;14:S35–S39.
9.
Fuster V, Badimon L, Badimon JJ, Chesebro JH: The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med 1992;326:310–318.
10.
Lam JY, Chesebro JH, Steele PM, Badimon L, Fuster V: Is vasospasm related to platelet deposition? Relationship in a porcine preparation of arterial injury in vivo. Circulation 1987;75:243–248.
11.
Chilian WM, Dellsperger KC, Layne SM, Eastham CL, Armstrong MA, Marcus ML, Heistad DD: Effects of atherosclerosis on the coronary microcirculation. Am J Physiol 1990;258:H529–H539.
12.
Sellke FW, Armstrong ML, Harrison DG: Endothelium-dependent vascular relaxation is abnormal in the coronary microcirculation of atherosclerotic primates. Circulation 1990;81:1586–1593.
13.
Maseri A, Crea F, Cianflone D: Myocardial ischemia caused by distal coronary vasoconstriction. Am J Cardiol 1992;70:1602–1605.
14.
Mulvany MJ, Halpern W: Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ Res 1977;41:19–26.
15.
Treasure CB, Klein JL, Vita JA, Manoukian SV, Renwick GH, Selwyn AP, Ganz P, Alexander RW: Hypertension and left ventricular hypertrophy are associated with impaired endothelium-mediated relaxation in human coronary resistance vessels. Circulation 1993;87:86–93.
16.
Treasure CB, Vita JA, Ganz P, Ryan TJ Jr, Schoen FJ, Vekshtein VI, Yeung AC, Mudge GH, Alexander RW, Selwyn AP, Fish RD: Loss of the coronary microvascular response to acetylcholine in cardiac transplant patients. Circulation 1992;86:1156–1164.
17.
Treasure CB, Manoukian SV, Klein JL, Vita JA, Nabel EG, Renwick GH, Selwyn AP, Alexander RW, Ganz P: Epicardial coronary artery responses to acetylcholine are impaired in hypertensive patients. Circ Res 1992;71:776–781.
18.
Harrison DG, Freiman PC, Armstrong ML, Marcus ML, Heistad DD: Alterations of vascular reactivity in atherosclerosis. Circ Res 1987;61:II74–II80.
19.
Treasure CB, Vita JA, Cox DA, Fish RD, Gordon JB, Mudge GH, Colucci WS, Sutton MG, Selwyn AP, Alexander RW, Ganz P: Endothelium-dependent dilation of the coronary microvasculature is impaired in dilated cardiomyopathy. Circulation 1990;81:772–779.
20.
Chester AH, O’Neil GS, Tadjkarimi S, Palmer RMJ, Moncada S, Yacoub MH: The role of nitric oxide in mediating endothelium dependent relaxations in the human epicardial coronary artery. Int J Cardiol 1990;29:305–309.
21.
Nakaike R, Shimokawa H, Yasutake H, Sumimoto H, Ito A, Numaguchi K, Egashira K, Takeshige K, Takeshita A: Effects of L-arginine analogues on vasomotion of isolated porcine coronary arteries. Am J Physiol 1997;268:H1966–H1972.
22.
Kalsner S: Cholinergic mechanisms in human coronary artery preparations: Implications of species differences. J Physiol 1985;358:509–526.
23.
Ginsburg R, Zera PH: Endothelial relaxant factor in the human epicardial coronary artery. Circulation 1984;70:122.
24.
Toda N: Mechanism of histamine actions in human coronary arteries. Circ Res 1987;61:280–286.
25.
Corr L, Burnstock G: Vasodilator response of coronary smooth muscle to the sympathetic co-transmitters noradrenaline and adenosine 5′-triphosphate. Br J Pharmacol 1991;104:337–342.
26.
Golino P, Piscione F, Willerson JT, Cappelli Bigazzi M, Focaccio A, Villari B, Indolfi C, Russolillo E, Condorelli M, Chiariello M: Divergent effects of serotonin on coronary-artery dimensions and blood flow in patients with coronary atherosclerosis and control patients. N Engl J Med 1991;324:641–648.
27.
McFadden EP, Clarke JG, Davies GJ, Kaski JC, Haider AW, Maseri A: Effect of intracoronary serotonin on coronary vessels in patients with stable angina and patients with variant angina. N Engl J Med 1991;324:648–654.
28.
Chester AH, O’Neil GS, Allen SP, Luu TN, Tadjkarimi S, Yacoub MH: Effect of endothelin on normal and diseased human coronary arteries. Eur J Clin Invest 1992;22:210–213.
29.
Chester AH, Dashwood MR, Clarke JG, Larkin SW, Davies GJ, Tadjkarimi S, Maseri A, Yacoub MH: Influence of endothelin on human coronary arteries and localization of its binding sites. Am J Cardiol 1989;63:1395–1398.
30.
Lerman A, Edwards BS, Hallett JW, Heublein DM, Sandberg SM, Burnett JC Jr: Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis. N Engl J Med 1991;325:997–1001.
31.
Lerman A, Holmes DR Jr, Bell MR, Garratt KN, Nishimura RA, Burnett JC Jr: Endothelin in coronary endothelial dysfunction and early atherosclerosis in humans. Circulation 1995;92:2426–2431.
32.
Bacon CR, Cary NRB, Davenport AP: Endothelin peptide and receptors in human atherosclerotic coronary artery and aorta. Circ Res 1996;79:794–801.
33.
Lerman A, Kubo SH, Tschumperlin LK, Burnett JC Jr: Plasma endothelin concentrations in humans with end-stage heart failure and after heart transplantation. J Am Coll Cardiol 1992;20:849–853.
34.
Kuo L, Davis MJ, Cannon MS, Chilian WM: Pathophysiological consequences of atherosclerosis extend into the coronary microcirculation. Restoration of endothelium-dependent responses by L-arginine. Circ Res 1992;70:465–476.
35.
Verbeuren TJ, Jordaens FH, Zonnekeyn LL, Van Hove CE, Coene MC, Herman AG: Effect of hypercholesterolemia on vascular reactivity in the rabbit. I. Endothelium-dependent and endothelium-independent contractions and relaxations in isolated arteries of control and hypercholesterolemic rabbits. Circ Res 1986;58:552–564.
36.
Simonsen U, Ehrnrooth E, Gerdes LU, Faergemann O, Buch J, Andreasen F, Mulvany MJ: Functional properties in vitro of systemic small arteries from rabbits fed cholesterol-rich diet for 12 weeks. Clin Sci 1991;80:119–129.
37.
Simonsen U, Prieto D, Nyborg NCB, Mulvany MJ: Effect of doxazosin on functional alterations of isolated coronary arteries from cholesterol-fed rabbits. J Pharm Pharmacol 1996;48:607–614.
38.
Simonsen U, Prieto D, Mulvany MJ, Ehrnrooth E, Korsgaard N, Nyborg NCB: Effect of induced hypercholesterolemia in rabbits on functional responses of isolated large proximal and small distal coronary arteries. Arterioscler Thromb 1992;13:380–392.
39.
Mankad PS, Chester AH, Yacoub MH: Role of potassium concentration in cardioplegic solutions in mediating endothelial damage. Ischaemic endothelial dysfunction after single or multidose cardioplegia. Ann Thorac Surg 1992;13:976–980.
40.
Saldanha C, Hearse DJ: Coronary vascular responsiveness to 5-hydroxytryptamine before and after infusion of hyperkalemic crystalloid cardioplegic solution in the rat heart. Possible evidence of endothelial damage. J Thorac Cardiovasc Surg 1989;98:783–787.
41.
Bodelsson M, Arneklo Nobin B, Chester AH, Tadjkarimi S, Tornebrandt K, Yacoub M: Differential effect of hypothermia on the vascular tone and reactivity of the human coronary artery and graft vessels. J Cardiovasc Surg 1991;32:288–294.
42.
Bandick NR, Roberts DE: Intrinsic alteration of the reactive properties of arteries during hypothermia. Cryobiology 1991;28:499–502.
43.
Egashira K, Inou T, Hirooka Y, Kai H, Sugimachi M, Suzuki S, Kuga T, Urabe Y, Takeshita A: Effects of age on endothelium-dependent vasodilation of resistance coronary artery by acetylcholine in humans. Circulation 1993;88:77–81.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.