Effects of Vasodilators on Coronary Vasospasm Induced by Endothelin in the Isolated Perfused Rat Heart

Kim, Si Oh; Kim, Dong Hwa; Moon, Cheol Won; Baek, Woon Yi; Hong, Jung Gil; Park, Jin Woong

Abstract

BACKGROUND: An endothelium derived vasoconstrictor peptide, endothelin, has been shown to be a potent coronary vascular constrictor. In the clinical settings of angina or myocardial ischemia, the endothelial injury of coronary artery can stimulate the endothelin production. In this study, the authors assessed the response to endothelin of the coronary artery in isolated rat heart and compared the relative effects of three vasodilators (nifedipine, adenosine, nitroprusside) on coronary vasospasm which was induced by endothelin.
METHODS
The isolated rat heart preparations (Langendorff model) were obtained from fourty male Sprague-Dawley rats (350-400 gm). Preparations were perfusated with Krebs-Hanseleit solution of (mM): NaCl 115, NaHCO3 25, KCl 4.7, CaCl2 2H2O 2.5, MgCl2 6H2O 1.2, KH2PO4 1.2, glucose 10. The perfusate was maintained at 37oC and aerated with carbogen (oxygen 95% and carbon dioxide 5%). The coronary perfusion was maintained at 80 cmH20 pressure and Latex balloon was positioned in left ventricle. After the preparations were stabilized, endothelin (10(-9) M) was added to perfusate for 5 minutes and followed the perfusion without vasodilators (control, n = 10) or with vasodilators (nifedipine, adenosine and nitroprusside 10(-7) M to 10(-6) M, n = 10 each) for 45 minutes. The left ventricular developed pressure (LDP) and heart rate (HR) was recorded and the coronary effluent (VOL) was collected to measure the unit volume and the CPK isoenzyme (CK-MB). Effects of the interventions were assessed using analysis of variance. All values are presented as means +/- SE.
RESULTS
VOL, HR and VDP were significantly reduced after infusion of 10(-9) M endothelin in 3 and 5 minutes. VOL was recovered efficiently after infusion of three vasodilators. Adenosine and nitroprusside groups showed superior recovery in the changes of rate pressure product (RPP) than in nifedipine group, which was significant reduced in VDP.
CONCLUSIONS
These results suggest that in the situation of endothelin induced severe coronary vasospasm, adenosine and nitroprusside effectively reversed the coronary vasospasm without severe myocardial depression.