Guanethidine-induced acute hypersensitivity to noradrenaline in anaesthetized rats

The changes in mean arterial blood pressure, heart rate and the respective noradrenaline dose-response curves after guanethidine sulphate (0.25, 1.25, 5, 20, and 40 mg/kg given intravenously) were studied in chloralose-urethane anesthetized adult rats. After transient changes a dose-dependent maximum fall of the blood pressure was observed 15 minutes after the administration of guanethidine. A fall in heart rate was observed after guanethidine sulphate 0.25 mg/kg, whereas 1,25, 5, 20, and 40 mg/kg initially increased the heart rate followed by a decrease to subnormal levels with minimum values 6-24 hours after guanethidine. Normalization of blood pressure and heart rate occurred within 24 hours and 96 hours, respcetively. Maximum dose-dependent enhancement of changes in blood pressure by noradrenaline 0.5 mug/kg was obtained approximately 15 minutes after guanethidine. Following guanethidine 40 mg/kg the response was increased by a factor 2, and normalization occurred within 96 hours. Fifteen minutes after guanethidine, significant changes in the response of the heart rate to noradrenaline 0.5 mug/kg were obtained with guanethidine 1.25, 5, and 20 mg/kg, whereas fully developed hypersensitivity after 20 and 40 mg/kg did not occur until 6-24 hours later. Following guanethidine 40 mg/kg the response was increased by a factor of 3, and normalization was observed after 96 hours. The present investigation has demonstrated different time-dependent patterns of the effect of guanethidine on blood pressure and heart rate responses to noradrenaline.