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Cyclosporin A-induced coronary artery vasoconstriction through myogenic and endothelium-dependent mechanisms
The exact mechanism of vascular toxicity of cyclosporin A (CSA) remains unknown. It has been reported that an impairment of endothelium-mediated vascular reactivity may be involved. We studied the response to intracoronary injections of acetylcholine (ACh) (30 ng/kg), adenosine (100 ng/kg), and nitr...
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Published in: | Circulation (New York, N.Y.) N.Y.), 1996-11, Vol.94 (9), p.308-311 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | The exact mechanism of vascular toxicity of cyclosporin A (CSA) remains unknown. It has been reported that an impairment of endothelium-mediated vascular reactivity may be involved.
We studied the response to intracoronary injections of acetylcholine (ACh) (30 ng/kg), adenosine (100 ng/kg), and nitroglycerin (NTG) (1.7 micrograms/kg) before and after intracoronary infusion of CSA (20 mg over 20 minutes) and of L-arginine (10 mg.kg-1.min-1). Experiments were performed on 11 open-chest dogs anesthetized and instrumented for measurements of coronary blood flow (CBF) in the left anterior descending (LAD) and left circumflex (LCx) coronary arteries, left ventricular dP/dt, mean aortic pressure, and coronary sinus pressure. CSA, L-arginine, ACh, adenosine, and NTG were injected into the LAD, and the LCx served as control. The increase in CBF in the LAD with ACh administration averaged 21 +/- 11 mL/min before CSA, 15 +/- 10 mL/min after CSA, and 15 +/- 8 mL/min during L-arginine injection (P = .2). Adenosine caused an increase in CBF in the LAD averaging 20 +/- 10 mL/min before CSA, 10 +/- 8 mL/min after CSA, and 17 +/- 12 mL/min during L-arginine injection (P = .004). NTG caused an increase in CBF in the LAD averaging 21 +/- 10 mL/min before CSA, 13 +/- 11 mL/min after CSA, and 14 +/- 7 after administration of L-arginine (P = .009).
These results suggest that direct intracoronary injection of CSA induces a vasoconstrictive response through endothelium-dependent and myogenic mechanisms. The muscarinic endothelial response was not affected by CSA, whereas the purinergic action of CSA was restored after L-arginine administration. |
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ISSN: | 0009-7322 1524-4539 |