CYCLOSPORINE-A-INDUCED CORONARY-ARTERY VASOCONSTRICTION THROUGH MYOGENIC AND ENDOTHELIUM-DEPENDENT MECHANISMS

Background The exact mechanism of vascular toxicity of cyclosporin A ( CSA) remains unknown. It has been reported that an impairment of endot helium-mediated vascular reactivity may be involved. Methods and Resul ts We studied the response to intracoronary injections of acetylcholin e (ACh) (30 ng/kg), adenosine (100 ng/kg), and nitroglycerin (NTG) (1. 7 mu g/kg) before and after intracoronary infusion of CSA (20 mg over 20 minutes) and of L-arginine (10 mg . kg(-1). min(-1)). Experiments w ere performed on 11 open-chest dogs anesthetized and instrumented for measurements of coronary blood flow (CBF) in the left anterior descend ing (LAD) and left circumflex (LCx) coronary arteries, left ventricula r dP/dt, mean aortic pressure, and coronary sinus pressure. CSA, L-arg inine, ACh, adenosine, and NTG were injected into the LAD, and the LCx served as control. The increase in CBF in the LAD with ACh administra tion 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 cau sed an increase in CBF in the LAD averaging 20 +/- 10 mL/min before CS A, 10 +/- 8 mL/min after CSA, and 17 +/- 12 mL/min during L-arginine i njection (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). Conclusions These results suggest that direct intracoronary injection of CSA induces a vasocons trictive response through endothelium-dependent and myogenic mechanism s. The muscarinic endothelial response was not affected by CSA, wherea s the purinergic action of CSA was restored after L-arginine administr ation.