THE INFLUENCE OF THE DOPA DECARBOXYLASE INHIBITOR Ro4-4602 ON THE URINARY EXCRETION OF CATECHOLAMINES IN COLD-STRESSED RATS

¹ Department of Pharmacology, University of Toronto, Toronto, Canada

Male Wistar rats were treated daily with time dopa decarboxylase inhibitor Ro4-4602 (N-(DL-seryl)-N'-(2,3,4-trihydroxybenzyl)-hydrazine), 420 mg/kg, and placed at 27°C for 2 days before being transferred to 4°C for several more days. Analysis of both tissue and urinary catecholamine levels under these conditions allowed a comparison of the effects of Ro4-4602 on catecholamine excretion under resting and coldstressed situations. Ro4-4602 produced a 30 to 50% fall in the norepinephrine contents of the heart, spleen and liver at both temperatures. Adrenal catecholamine levels were only depressed by the drug in the cold-exposed rats. Ro4-4602 did not influence the catecholamine excretion of rats at 27°C, but did significantly diminish the cold-induced increase in norepinephrine excretion. These results suggest that inhibition of dopa decarboxylase does not influence the relatively slow synthesis of catecholamines at 27°C but does impede the cold-induced increase in norepinephrine biosynthesis. An increase in urinary epinephrine levels accompanied the decreased excretion of norepinephrine in the cold. This increased epinephrine release is presumably responsible for the maintenance of life because most adrenalectomized rats (treated with corticoids) that were administered Ro4-4602 died within 3 days of being exposed to 4°C, whereas all intact drug-treated rats survived at least 6 days at this temperature.