EFFECTS OF NISOLDIPINE UPON ENDOTHELIAL DYSFUNCTION FOLLOWING ISCHEMIC AND PEROXIDATIVE INJURY IN THE PERFUSED RAT-HEART

Objective: Previous studies showed that treatment of hearts with nisol dipine improves recovery of cardiac function following ischaemia, impr oves reperfusion, and reduces the constrictor sensitivity to endotheli n. The aim of the present study was to assess the reduction in vasodil ator responses that occurs following ischaemia and reperfusion or afte r oxidative stress, and to determine whether nisoldipine treatment imp roves these dilator responses. Methods: Isolated perfused rat hearts w ere studied. Coronary vessels were constricted by the addition of U466 19 and dilator responses were determined with the addition of acetylch oline (endothelium dependent) or glyceryl trinitrate (endothelium inde pendent). Responses were compared before and after low flow ischaemia (20%, 30 min) and reperfusion (30 min), or treatment with tert-butyl h ydroperoxide (tBHP) (0.9 mM, 12 min, 30 min wash). Results: The additi on of U46619 caused a prolonged increase in perfusion pressure of 50 t o 70 mm Hg which was not significantly different before and after trea tment. Dilatation responses to acetylcholine were significantly reduce d following ischaemia and reperfusion (34% of preischaemic values) or tBHP (47.6% of pre-tBHP values), while responses to glyceryl trinitrat e were not significantly changed. In contrast, when hearts were perfus ed with nisoldipine, the responses to acetylcholine were significantly improved (88% of preischaemic values with 5 nM nisoldipine, and 68% t o 78% of pre-tBHP values with 0.5 nM to 5 nM nisoldipine). Responses t o acetylcholine following tBHP were not significantly improved when he arts were perfused with verapamil (5 nM 43.5%, 5 muM 32%, of pre-tBHP values), or diltiazem (5 nM 37%, 5 muM 31%, of pre-tBHP values). Concl usions: Ischaemia and reperfusion or oxidative stress reduced endothel ium dependent responses, but not endothelium independent responses. Ni soldipine reduced the injury to endothelial cell function associated w ith ischaemia and reperfusion or oxidative stress.