Guanethidine‐induced Acute Hypersensitivity to Noradrenaline in Anaesthetized Rats

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Abstract
The changes in mean arterial blood pressure, heart rate and the respective noradrenaline dose-response curves after guanethidine sulfate (0.25, 1.25, 5, 20 and 40 mg/kg, i.v.) were studied in chloralose-urethane anesthetized adult rats. After transient changes a dose-dependent maximum fall of the blood pressure was observed 15 min after guanethidine administration. A fall in heart rate was observed after guanethidine sulfate 0.25 mg/kg; 1.25, 5, 20 and 40 mg/kg guanethidine initially increased the heart rate followed by a decrease to subnormal levels with minimum values 6-24 h. Blood pressure and heart rate normalization occurred within 24 h and 96 h, respectively. Maximum dose-dependent enhancement of blood pressure changes by noradrenaline 0.5 .mu.g/kg was obtained approximately 15 min after guanethidine. Following guanethidine 40 mg/kg the response was increased by a factor 2, and normalization occurred within 96 h. Fifteen min after guanethidine, significant changes in the heart rate response to noradrenaline 0.5 .mu.g/kg were obtained with guanethidine 1.25, 5 and 20 mg/kg; fully developed hypersensitivity after 20 and 40 mg/kg did not occur until 6-24 h later. Following guanethidine 40 mg/kg the response was increased by a factor of 3, and normalization was observed after 96 h. Different time-dependent patterns of the effect of guanethidine on blood pressure and heart rate responses to noradrenaline were therefore demonstrated.

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