BACKGROUND. Serotonin, a major product of platelet activation, has potent vasoactive effects in animal models, but its role in human coronary artery disease remains largely speculative. METHODS. Using quantitative coronary angiography, we compared the effects of the intracoronary infusion of graded concentrations of serotonin (10(-7) to 10(-4) mol per liter) on coronary vessels in two groups of patients with different clinical presentations of coronary disease (nine with stable angina and five with variant angina), with the effects in a control group of eight subjects with normal vessels on angiography. RESULTS. Normal coronary vessels had a biphasic response to intracoronary serotonin: dilation at concentrations up to 10(-5) mol per liter, but constriction at 10(-4) mol per liter. Vessels in patients with stable angina constricted at all concentrations, with mean (+/- SEM) maximal decreases in diameter of 23.9 +/- 3.6, 33.1 +/- 3.9, and 41.7 +/- 3.1 percent from base line in proximal, middle, and distal segments at a serotonin concentration of 10(-4) mol per liter. Smooth segments constricted more than irregular segments (42.0 +/- 4.6 vs. 21.1 +/- 1.6 percent). Four patients with stable angina had a marked reduction in collateral filling. All the patients with stable angina had angina during the intracoronary infusion of serotonin, and electrocardiographic changes were noted in six. All the patients with variant angina had angina, electrocardiographic changes, and localized occlusive epicardial coronary-artery spasm at concentrations of 10(-6) (n = 2) or 10(-5) (n = 3) mol per liter. CONCLUSIONS. Patients with stable coronary disease do not have the normal vasodilator response to intracoronary serotonin, but rather have progressive constriction, which is particularly intense in small distal and collateral vessels. Patients with variant angina have occlusive coronary-artery spasm at a dose that dilates normal vessels and causes only slight constriction in vessels from patients with stable angina. These findings suggest that serotonin, released after the intracoronary activation of platelets, may contribute to or cause myocardial ischemia in patients with coronary artery disease.
Source Information
Cardiovascular Research Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
This article has been cited by other articles:
Mishra, P. K.
(2006). Variations in presentation and various options in management of variant angina.. Eur. J. Cardiothorac. Surg.
29: 748-759
[Abstract][Full Text]
Herman, A. G., Moncada, S.
(2005). Therapeutic potential of nitric oxide donors in the prevention and treatment of atherosclerosis. Eur Heart J
26: 1945-1955
[Abstract][Full Text]
Redfern, W.S., Carlsson, L., Davis, A.S., Lynch, W.G., MacKenzie, I., Palethorpe, S., Siegl, P.K.S., Strang, I., Sullivan, A.T., Wallis, R., Camm, A.J., Hammond, T.G.
(2003). Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc Res
58: 32-45
[Abstract][Full Text]
Kawano, H., Motoyama, T., Yasue, H., Hirai, N., Waly, H. M., Kugiyama, K., Ogawa, H.
(2002). Endothelial function fluctuates with diurnal variation in the frequency of ischemic episodes in patients with variant angina. J Am Coll Cardiol
40: 266-270
[Abstract][Full Text]
Springer, S., Fife, A., Lawson, W., Hui, J. C.K., Jandorf, L., Cohn, P. F., Fricchione, G.
(2001). Psychosocial Effects of Enhanced External Counterpulsation in the Angina Patient: A Second Study. Psychosomatics
42: 124-132
[Abstract][Full Text]
Ishida, T., Kawashima, S., Hirata, K.-i., Sakoda, T., Shimokawa, Y., Miwa, Y., Inoue, N., Ueyama, T., Shiomi, M., Akita, H., Yokoyama, M.
(2001). Serotonin-Induced Hypercontraction Through 5-Hydroxytryptamine 1B Receptors in Atherosclerotic Rabbit Coronary Arteries. Circulation
103: 1289-1295
[Abstract][Full Text]
Yang, Q., Scalbert, E., Delagrange, P., Vanhoutte, P. M., O'Rourke, S. T.
(2001). Melatonin potentiates contractile responses to serotonin in isolated porcine coronary arteries. Am. J. Physiol. Heart Circ. Physiol.
280: H76-H82
[Abstract][Full Text]
Spyrou, N., Khan, M. A., Rosen, S. D., Foale, R., Davies, D. W., Sogliani, F., Stanbridge, R. D. L., Camici, P. G.
(2000). Persistent but reversible coronary microvascular dysfunction after bypass grafting. Am. J. Physiol. Heart Circ. Physiol.
279: H2634-H2640
[Abstract][Full Text]
Al-Saadi, N., Nagel, E., Gross, M., Schnackenburg, B., Paetsch, I., Klein, C., Fleck, E.
(2000). Improvement of myocardial perfusion reserve early after coronary intervention: assessment with cardiac magnetic resonance imaging. J Am Coll Cardiol
36: 1557-1564
[Abstract][Full Text]
Kaufmann, P. A., Gnecchi-Ruscone, T., Schafers, K. P., Luscher, T. F., Camici, P. G.
(2000). Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia. J Am Coll Cardiol
36: 103-109
[Abstract][Full Text]
Whan Lee, C., Park, S.-W., Cho, G.-Y., Hong, M.-K., Kim, J.-J., Kang, D.-H., Song, J.-K., Lee, H.-J., Park, S.-J.
(2000). Pressure-derived fractional collateral blood flow: a primary determinant of left ventricular recovery after reperfused acute myocardial infarction. J Am Coll Cardiol
35: 949-955
[Abstract][Full Text]
L'Abbate, A., Sambuceti, G., Haunso, S., Schneider-Eicke, J.
(1999). Methods for evaluating coronary microvasculature in humans. Eur Heart J
20: 1300-1313
Herrington, D. M., Werbel, B. L., Riley, W. A., Pusser, B. E., Morgan, T. M.
(1999). Individual and combined effects of estrogen/progestin therapy and lovastatin on lipids and flow-mediated vasodilation in postmenopausal women with coronary artery disease. J Am Coll Cardiol
33: 2030-2037
[Abstract][Full Text]
Eguchi, H., Ikeda, H., Murohara, T., Yasukawa, H., Haramaki, N., Sakisaka, S., Imaizumi, T.
(1999). Endothelial Injuries of Coronary Arteries Distal to Thrombotic Sites : Role of Adhesive Interaction Between Endothelial P-Selectin and Leukocyte Sialyl LewisX. Circ. Res.
84: 525-535
[Abstract][Full Text]
Markovitz, J. H., Tolbert, L., Winders, S. E.
(1999). Increased Serotonin Receptor Density and Platelet GPIIb/IIIa Activation Among Smokers. Arterioscler. Thromb. Vasc. Bio.
19: 762-766
[Abstract][Full Text]
Egermayer, P., Town, G I., Peacock, A. J
(1999). Role of serotonin in the pathogenesis of acute and chronic pulmonary hypertension. Thorax
54: 161-168
[Full Text]
Suzuki, H., Kawai, S., Aizawa, T., Kato, K., Sunayama, S., Okada, R., Yamaguchi, H.
(1999). Histological evaluation of coronary plaque in patients with variant angina: relationship between vasospasm and neointimal hyperplasia in primary coronary lesions. J Am Coll Cardiol
33: 198-205
[Abstract][Full Text]
Ishida, T., Hirata, K.-i., Sakoda, T., Kawashima, S., Akita, H., Yokoyama, M.
(1999). Identification of mRNA for 5-HT1 and 5-HT2 receptor subtypes in human coronary arteries. Cardiovasc Res
41: 267-274
[Abstract][Full Text]
Takata, S., Shimakura, A., Sakagami, S., Nakamura, Y., Ohkuwa, H., Kobayashi, K.-i., Nagai, H.
(1998). Enhanced Insulin Response to Oral Glucose Load in Patients with Angina Pectoris Associated with ST Segment Elevation in the Absence of Epicardial Coronary Arterial Obstruction. ANGIOLOGY
49: 815-826
[Abstract]
Bhagat, K.
(1998). Endothelial function and myocardial infarction. Cardiovasc Res
39: 312-317
[Full Text]
Bychkov, R., Gollasch, M., Steinke, T., Ried, C., Luft, F. C., Haller, H.
(1998). Calcium-Activated Potassium Channels and Nitrate-Induced Vasodilation in Human Coronary Arteries. J. Pharmacol. Exp. Ther.
285: 293-298
[Abstract][Full Text]
Baker, W. F. JR
(1998). Thrombosis and Hemostasis in Cardiology: Review of Pathophysiology and Clinical Practice (Part I). CLIN APPL THROMB HEMOST
4: 51-75
[Abstract]
Goldberg, R. J.
(1998). Selective Serotonin Reuptake Inhibitors: Infrequent Medical Adverse Effects. Arch Fam Med
7: 78-84
[Abstract][Full Text]
FARACI, F. M., HEISTAD, D. D.
(1998). Regulation of the Cerebral Circulation: Role of Endothelium and Potassium Channels. Physiol. Rev.
78: 53-97
[Abstract][Full Text]
Hayreh, S. S., Piegors, D. J., Heistad, D. D.
(1997). Serotonin-Induced Constriction of Ocular Arteries in Atherosclerotic Monkeys: Implications for Ischemic Disorders of the Retina and Optic Nerve Head. Arch Ophthalmol
115: 220-228
[Abstract]
Liuzzo, G., Biasucci, L. M., Rebuzzi, A. G., Gallimore, J. R., Caligiuri, G., Lanza, G. A., Quaranta, G., Monaco, C., Pepys, M. B., Maseri, A.
(1996). Plasma Protein Acute-Phase Response in Unstable Angina Is Not Induced by Ischemic Injury. Circulation
94: 2373-2380
[Abstract][Full Text]
Kugiyama, K., Yasue, H., Okumura, K., Ogawa, H., Fujimoto, K., Nakao, K., Yoshimura, M., Motoyama, T., Inobe, Y., Kawano, H.
(1996). Nitric Oxide Activity Is Deficient in Spasm Arteries of Patients With Coronary Spastic Angina. Circulation
94: 266-272
[Abstract][Full Text]
Kadokami, T., Egashira, K., Kuwata, K., Fukumoto, Y., Kozai, T., Yasutake, H., Kuga, T., Shimokawa, H., Sueishi, K., Takeshita, A.
(1996). Altered Serotonin Receptor Subtypes Mediate Coronary Microvascular Hyperreactivityin Pigs With Chronic Inhibitionof Nitric Oxide Synthesis. Circulation
94: 182-189
[Abstract][Full Text]
White, C. W.
(1996). Simplicity's Virtue Scorned : Precision Comes to TIMI Flow Grading and the Results Are . . . Surprising. Circulation
93: 853-856
[Full Text]
Ozaki, Y., Keane, D., Serruys, P. W.
(1995). Progression and Regression of Coronary Stenosis in the Long-term Follow-up of Vasospastic Angina. Circulation
92: 2446-2456
[Abstract][Full Text]
Kaski, J. C., Chester, M. R., Chen, L., Katritsis, D.
(1995). Rapid Angiographic Progression of Coronary Artery Disease in Patients With Angina Pectoris : The Role of Complex Stenosis Morphology. Circulation
92: 2058-2065
[Abstract][Full Text]
Bauters, C., Asahara, T., Zheng, L. P., Takeshita, S., Bunting, S., Ferrara, N., Symes, J. F., Isner, J. M.
(1995). Recovery of Disturbed Endothelium-Dependent Flow in the Collateral-Perfused Rabbit Ischemic Hindlimb After Administration of Vascular Endothelial Growth Factor. Circulation
91: 2802-2809
[Abstract][Full Text]
Chen, L., Chester, M. R., Redwood, S., Huang, J., Leatham, E., Kaski, J. C.
(1995). Angiographic Stenosis Progression and Coronary Events in Patients With `Stabilized' Unstable Angina. Circulation
91: 2319-2324
[Abstract][Full Text]
Zeiher, A. M., Goebel, H., Schachinger, V., Ihling, C.
(1995). Tissue Endothelin-1 Immunoreactivity in the Active Coronary Atherosclerotic Plaque : A Clue to the Mechanism of Increased Vasoreactivity of the Culprit Lesion in Unstable Angina. Circulation
91: 941-947
[Abstract][Full Text]
Uren, N. G., Crake, T., Lefroy, D. C., de Silva, R., Davies, G. J., Maseri, A.
(1994). Reduced Coronary Vasodilator Function in Infarcted and Normal Myocardium after Myocardial Infarction. NEJM
331: 222-227
[Abstract][Full Text]
Nagai, H., Nakamura, Y., Takata, S., Kobayashi, K.-i.
(1994). Angina Pectoris Associated with ST Segment Elevation in the Absence of Epicardial Coronary Arterial Obstruction: Case Reports. ANGIOLOGY
45: 391-397
[Abstract]
Golino, P., Piscione, F., Benedict, C. R., Anderson, H. V., Cappelli-Bigazzi, M., Indolfi, C., Condorelli, M., Chiariello, M., Willerson, J. T.
(1994). Local Effect of Serotonin Released during Coronary Angioplasty. NEJM
330: 523-528
[Abstract][Full Text]
Ware, J. A., Heistad, D. D.
(1993). Platelet-Endothelium Interactions. NEJM
328: 628-635
[Full Text]
Minor, R. L. Jr., Scott, B. D., Brown, D. D., Winniford, M. D.
(1991). Cocaine-induced Myocardial Infarction in Patients with Normal Coronary Arteries. ANN INTERN MED
115: 797-806
[Abstract]
Tanner, F. C, Tschudi, M. R, Luscher, T. F
(1991). Endothelium, lipoproteins and atherosclerotic vascular disease. Vasc Med
2: 161-176
[Abstract]
(1991). SEROTONIN'S ROLE IN ACUTE CORONARY ISCHEMIA. JWatch General
1991: 7-7
[Full Text]
Previous
