EFFECT OF MERALLURIDE ON SOLUTE AND WATER EXCRETION IN HYDRATED MAN: COMMENTS ON SITE OF ACTION*

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Abstract
In control studies in hydrated subjects it was demonstrated that the infusion of a "nonspecific solute diuretic," such as mannitol, sulfate, urea or aminophylline produced a consistent increase in CH2o as COsm rose. In 21 comparably hydrated subjects, the intravenous administration of meralluride caused a two-phase response. The first phase was characterized by a prompt increase in V, CH2O and Cosm with peak increments averaging 5.9, 4.4 and 1.5 ml per minute, respectively. These changes tended to disappear within 45 to 60 minutes. Thereafter, there occurred a much larger and more sustained diuresis. In 17 of these subjects, the peak increments in V and COsm averaged 8.9 and 9.2 ml per minute, respectively, so that CH2O values during this maximal diuresis were virtually identical with those calculated during the pre-injection control periods. In 4 of these subjects, CH2O fell to levels below control values immediately prior to the development of the major portion of the solute diuresis, but again remained relatively fixed during the saluresis. In 10 of the 21 subjects described above, a nonspecific solute diuretic was administered during the delayed phase of meral-luride diuresis. In 7 of these experiments, a further increase in Cosm, averaging 5.2 ml per minute, produced an average increase in CH2o of 3.9 ml per minute. The first phase of meralluride response seems best explained by the theophylline contained within meralluride. Two alternate hypotheses are presented to explain the characteristics of the sustained phase of meralluride diuresis.