Summary
Sympathetic stimulation by cold-pressor testing induces a complex interplay between adrenergic receptor stimulation, humoral and local metabolic factors, and alterations in coronary perfusion pressure. Since the endothelium importantly modulates the effect of neurohumoral stimulation, we evaluated the coronary hemodynamic determinants of epicardial artery vasomotor responses to cold-pressor testing in 12 normal patients with intact endothelial function, and in 20 patients with early atherosclerosis, demonstrating a dysfunctional endothelium. Endothelial function was assessed by intracoronary infusion of the endothelium-dependent dilator acetylcholine. Vasomotor responses were examined by quantitative coronary angiography and continuous intracoronary flow velocity measurements using a Doppler catheter. All coronary artery segments demonstrating a dilator response to intracoronary acetylcholine also vasodilated in response to cold-pressor testing by 19.7±8.2% (mean ±1 SD). In contrast, all arteries with evidence of atherosclerosis demonstrated a vasoconstrictor response during cold pressor testing with an area reduction by 18.4±7.5%. The systemic hemodynamic variables heart rate and mean aortic pressure increased by comparable amounts in both groups of patients during cold pressor testing, indicating comparable increases in myocardial workloads. There was a significant positive relation between increases in blood flow and changes in arterial luminal area. Increases in blood flow were closely related to increases in mean aortic pressure in normal epicardial vessels, but this relation was blunted in vessels with a dysfunctional endothelium. Estimated shear stress changes within the epicardial conductance vessels were significantly lower in normal compared to atherosclerotic arteries.
Thus, the increase in coronary blood flow is an important hemodynamic determinant of epicardial artery dilation in normal arteries during cold pressor testing. On the other hand, the vasodilator response limits increases in shear stress for a given increase in blood flow. In contrast, the failure of atherosclerotic arteries to dilate, despite increased myocardial demands, exaggerates increases in local shear stress in relation to changes in flow.
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
Bassenge E, Busse R (1988) Endothelial modulation of coronary tone. Progr Cardiovasc Dis 30:349–380
Bossaler C, Habib GB, Yamamoto H, Williams C, Wells S, Henry PD (1987) Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta. J Clin Invest 79:170–174
Chester AH, O’Neil GS, Moncada S, Tadjkarimi S, Yacoub MH (1990). Low basal and stimulated release of nitric oxide in atherosclerotic epicardial coronary arteries. Lancet II:897–900
Cocks TM, Angus JA (1983) Endothelium-dependent relaxation of coronary arteries by noradrenaline and serotonin. Nature 305:627–630
Cohen RA, Shepherd JT, Vanhoutte PM (1983) Inhibitory role of the endothelium in the response of isolated coronary arteries to platelets. Science 221:273–274
Cornhill JF, Roach MR (1976) A quantitative study of the localization of atherosclerotic lesions in the rabbit aorta. Atherosclerosis 23:489–501
Cox DA, Vita JA, Treasure CB, Fish RD, Alexander RW, Ganz P, Selwyn AP (1989) Atherosclerosis impairs flow-mediated dilation of coronary arteries in humans. Circulation 80:458–465
Dewey CF, Bussolari SR, Gimbrone MA, Davies PF (1981) The dynamic response of vascular endothelial cells to fluid shear stress. J Biomech Eng 103:177–185
Drexler H, Zeiher AM, Wollschläger H, Meinertz T, Just H, Bonzel T (1989) Flow-dependent coronary artery dilatation in humans. Circulation 80:466–474
Feigl EO (1987) The paradox of adrenergic coronary vasoconstriction. Circulation 76:737–745
Frangos JA, Eskin SG, McIntire LV (1985) Flow effects on prostacyclin production by cultured human endothelial cells. Science 227:1477–1479
Freiman PC, Mitchell GC, Heistad DD, Armstrong ML, Harrison DG (1986) Atherosclerosis impairs endothelium-dependent vascular relaxation to acetylcholine and thrombin in primates. Circ Res 58:783–789
Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376
Gaglione A, Hess OM, Corin WJ, Ritter M, Grimm J, Krayenbühl HP (1987) Is there coronary vasoconstriction after intracoronary beta-adrenergic blockade in patients with coronary artery disease. J Am Coll Cardiol 10:299–310
Gordon JB, Ganz P, Nabel EG, Fish RD, Zebede J, Mudge GH, Alexander RW, Selwyn AP (1989) Atherosclerosis influences the vasomotor response of epicardial arteries to exercise. J Clin Invest 83:1946–1952
Griffith TM, Edwards DH (1990) Myogenic autoregulation of flow may be inversely related to endothelium-derived relaxing factor activity. Am J Physiol 258:H1171–H1180
Holtz J, Förstermann U, Pohl U, Giesler M, Bassenge E (1984) Flow-dependent, endothelium-mediated dilation of epicardial coronary arteries in conscious dogs: effects of cyclooxygenase inhibition. J Cardiovasc Pharmacol 6:1161–1169
Houston DS, Shepherd JT, Vanhoutte PM (1986) Aggregating human platelets cause direct contraction and endothelium-dependent relaxation of isolated canine coronary arteries: role of serotonin, thromboxane A2 and adenine nucleotides. J Clin Invest 78:539–544
Katusic ZS, Shepherd JT, Vanhoutte PM (1987) Endothelium-dependent contraction to stretch in canine basilar arteries. Am J Physiol 252:H671–H673
Ku DN, Giddens DG, Zarins CK, Glagov S (1985) Pulsatile flow and atherosclerosis in human carotid bifurcation: positive correlation between plaque location and low and oscillating shear stress. Arteriosclerosis 5:293–302
Lansman JB, Hallam TJ, Rink TJ (1987) Single stretch-activated ion channels in vascular endothelial cells as mechanostransducers. Nature 325:811–813
Levesque MJ, Liepsch D, Moravec S, Nerem RM (1986) Correlation of endothelial cell shape and wall shear stress in a stenosed dog aorta. Arteriosclerosis 6:220–229
Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, Ganz P (1986) Paradoxical vascoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 315:1046–1051
Lutz RJ, Cannon JN, Bischoff KB, Dedrick RL, Stiles RK, Fry DL (1977) Wall shear stress distribution in a model canine artery during steady flow. Circ Res 41:391–399
Miller VM, Vanhoutte PM (1985) Endothelium-dependent contractions to arachidonic acid are mediated by products of cyclooxygenase. Am J Physiol 248:H432–H437
Milnor WR (1982) Hemodynamics. William & Wilkins, Baltimore, pp 49–51
Myers PR, Banitt PF, Guerra R, Harrison DG (1989) Characteristics of canine resistance arteries: importance of endothelium. Am J Physiol 247:H603–H610
Nabel EG, Ganz P, Gordon JB, Alexander RW, Selwyn AP (1988) Dilation of normal and constriction of atherosclerotic coronary arteries caused by the cold pressor test. Circulation 77:43–52
Olesen SP, Clapham DE, Davies PF (1988) Hemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature 331:169–170
Pohl U, Holtz J, Busse R, Bassenge E (1986) Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension 8:37–44
Pohl U, Lamontagne D (1991) Impaired tissue perfusion after inhibition of endothelium-derived nitric oxide. Bas Res Cardiol 86 (Suppl 2):97–105
Rubanyi GM, Romero JC, Vanhoutte PM (1986) Flow-induced release of endothelium-derived relaxing factor. Am J Physiol 250:H1145–0049
Shimokawa H, Vanhoutte PM (1989) Impaired endothelium-dependent relaxation to aggregating platelets and related vasoactive substances in porcine coronary arteries in hyper-cholesterolemia and atherosclerosis. Circ Res 64:900–914
Vanhoutte PM, Houston DS (1985) Platelets, endothelium, and vasospasm. Circulation 72:728–738
Vita JA, Treasure CB, Fish RD, Yeung AC, Vekshtein VI, Ganz P, Selwyn AP (1990) Endothelial dysfunction leads to increased coronary constriction to catecholamines in patients with early atherosclerosis (abstract). J Am Coll Cardiol 15:158A
Vita JA, Treasure CB, Ganz P, Cox DA, Fish RD, Selwyn AP (1989) Control of shear stress in the epicardial coronary arteries of humans: impairment by atherosclerosis. J Am Coll Cardiol 14:1193–1199
Vita JA, Treasure CB, Nabel EG, McLenachan JM, Fish RD, Yeung AC, Vekshtein VI, Selwyn AP, Ganz P (1990) Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation 81:491–497
Wollschläger H, Lee P, Zeiher AM, Solzbach U, Bonzel T, Just H (1986) Improvement of quantitative angiography by exact calculation of radiological magnification factors. Comput Cardiol: 483-486
Yasue H, Matsuyama K, Matsuyama K, Okumura K, Morikami Y, Ogawa H (1990) Responses of angiographically normal human coronary arteries to intracoronary injection of acetylcholine by age and segment. Circulation 81:482–490
Young MA, Vatner SF (1986) Enhanced adrenergic constriction of iliac artery with removal of endothelium in conscious dog. Am J Physiol 250:H892–897
Zeiher AM, Drexler H, Wollschläger H, Saurbier B, Just H (1989) Coronary vasomotion in response to sympathetic stimulation in humans: importance of the functional integrity of the endothelium. J Am Coll Cardiol 14:1181–1190
Zeiher AM, Drexler H, Wollschläger H, Just H (1991) Modulation of coronary vasomotor tone in humans: progressive endothelial dysfunction with different early stages of coronary atherosclerosis. Circulation 83:391–401
Zeiher AM, Drexler H, Wollschläger H, Just H (1989) Preserved flow mediated vasodilation despite acetylcholine-induced vasoconstriction in atherosclerotic coronary arteries in man (abstract). J Am Coll Cardiol 13:132A
Zeiher AM, Siegemund M, Wollschläger H, Drexler H (1990) Persistence of sympathetic-mediated constriction of epicardial arteries after local α-blockade in patients with coronary artery disease (abstract). Circulation 82 (suppl III):II–300
Zeiher AM, Schächinger V, Weitzel SH, Wollschläger H, Just H (1991) Intracoronary thrombus formation causes focal vasoconstriction of epicardial arteries in patients with coronary artery disease. Circulation (in press)
Zeiher AM, Drexler H, Wollschläger H, Just H (1990) Endothelial dysfunction alters the linkage of myocardial oxygen demand to microvascular tone in humans (abstract). Circulation 82 (suppl III):III–247
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt
About this paper
Cite this paper
Zeiher, A.M., Drexler, H. (1991). Coronary hemodynamic determinants of epicardial artery vasomotor responses during sympathetic stimulation in humans. In: Drexler, H., Zeiher, A.M., Bassenge, E., Just, H. (eds) Endothelial Mechanisms of Vasomotor Control. Steinkopff. https://doi.org/10.1007/978-3-642-72461-9_20
Download citation
DOI: https://doi.org/10.1007/978-3-642-72461-9_20
Publisher Name: Steinkopff
Print ISBN: 978-3-642-72463-3
Online ISBN: 978-3-642-72461-9
eBook Packages: Springer Book Archive