Effect of Neurohypophysectomy on Antidiuretic Activity of Substituted 3-Hydroxy Cinchoninic Acids in the Rat

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Abstract
Derivatives of 3-hydroxy-cinchoninic acid are antidiuretic in the rat, dog and man. Two of these compounds were studied before and after neurohypophysectomy in the rat; nicotine and pitressin were also studied. In 10 rats with a partial neurohypophysectomy (19-71% of the neural lobe remained) all developed diabetes insipidus. In 9 of these the antidiuretic effects of 3-hydroxy-2-phenylcinchoninic acid (HPC) and nicotine were abolished. In 7 the antidiuretic effect of a much more active compound, 7-chloro-3-hydroxy-2-phenylcinchoninic acid, was likewise abolished. All 10 animals responded to pitressin after operation. It is concluded that the antidiuretic activity of these compounds is mediated, in this species, via the hypothalamo neurohypophyseal system. Another series of 6 rats with total ablation of the anterior lobe and 42-76% remaining neural lobe was studied. These animals had mild tendencies toward polydypsia but not frank diabetes insipidus. When desoxycorticosterone was administered for several days it was possible to obtain a water diuresis. Under these conditions the animals responded with an antidiuretic effect to both HPC and to nicotine. Cell counts of the para-ventricular and supraoptic nuclei following these operations are given. The paraventricular group is virtually abolished after total removal of the anterior lobe. Other results agree with the concept of at least partial dependence of hypothalamic nuclei on the neural lobe.