An inhibitory effect of verapamil and diltiazem on the release of noradrenaline from ischaemic and reperfused hearts

Abstract

We have investigated whether Ca2+ antagonists reduce the amount of noradrenaline lost from the myocardium during periods of ischaemia and reperfusion. Hearts obtained from adult, male normotensive Sprague Dawley, Wistar Kyoto and spontaneously hypertensive rats were perfused in the Langendorff mode at 37 degrees C before being made globally ischaemic for either 15, 30 or 60 min. Some of the hearts were reperfused, and in some ECG records were made. 90-min normothermic aerobic perfusion failed to cause a significant change in left ventricular noradrenaline content. In Sprague Dawley and spontaneously hypertensive, but not Wistar Kyoto rats, 15 min ischaemia followed by 1 min reperfusion caused a significant (P less than 0.05) loss of noradrenaline. Extending the ischemic episode to 60 min resulted in a further loss of noradrenaline (P less than 0.005) in the Sprague Dawley, Wistar Kyoto and spontaneously hypertensive hearts and this loss was exacerbated upon reperfusion. Neither dl verapamil (2.5 X 10(-8) to 1.2 X 10(-6) mol/l) nor diltiazem (0.25 to 1.25 X 10(-6) mol/l) caused any change in the noradrenaline content of the aerobically perfused hearts. (1.25 X 10(-1) to 1.2 X 10(-1) mol/l) verapamil abolished the release of noradrenaline caused by 15 min ischaemia and reduced the release caused by 60 min ischaemia and 15 min reperfusion. The dose-response curve for verapamil was bell-shaped and the activity resided in the l form. Diltiazem (1.25 X 10(-6) mol/l but not 2.5 X 10(-1) mol/l) also abolished the loss of noradrenaline caused by short periods of ischaemia and reperfusion.