Inhibition of antidiuretic hormone secretion by diphenylhydantoin.
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Biomedical subjects
Publications and source records attributed to C R Kleeman.
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The effect of hypermagnesemia, produced by MgCl(2) infusion, on the activity of parathyroid glands, as assessed by changes in levels of serum calcium (S(Ca)) and in the fraction of filtered phosphate excreted (C(P)/C(Cr)), was studied in 11 intact and 4 thyroparathyroidectomized (T-PTX) dogs. To exclude the effect of diurnal variation in C(P)/C(Cr) on the results, studies were initiated in both morning and afternoon hours and each study with MgCl(2) infusion was paired with a control experiment in the same dog not receiving MgCl(2). During MgCl(2) infusion, serum phosphorus rose progressively. Despite this rise, the levels of C(P)/C(Cr) fell in all experiments and were significantly different from values observed at the same time of the day in the paired control experiments. The concentrations of total S(Ca) fell by 1.0-2.4 mg/100 ml with a proportional decrease in the levels of the diffusible and ionized fractions. The pattern of the fall in C(P)/C(Cr) during MgCl(2) resembled that observed after CaCl(2) infusion (seven dogs) and that which acutely followed thyroparathyroidectomy (seven dogs). When parathyroid extract was given to dogs receiving MgCl(2) infusion both C(P)/C(Cr) and S(Ca) rose, and MgCl(2) infusion did not affect C(P)/C(Cr) and S(Ca) in T-PTX dogs. These results indicate that hypermagnesemia suppresses the activity of the parathyroid glands, probably, by inhibiting production and (or) release of the hormone, without interfering with end-organ response. An increase in serum magnesium of 1.7-2.0 mg/100 ml was capable of producing the suppressive effect. Evaluation of the effect of simultaneous modest hypocalcemia and hypermagnesemia suggests that a decrease in the level of serum calcium is more potent than an increase in the concentration of serum magnesium in the regulation of parathyroid activity.
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Na efflux of rabbit RBC is approximately 10 mmoles/kg wet weight. hr. One-half of this consists of a ouabain-insensitive exchange diffusion component. Ouabain inhibits 2.5 mmoles/kg.hr of Na efflux. K influx is 3.0 mmoles/kg.hr; 2.2 mmoles/kg.hr are inhibited by ouabain. In contrast with human RBC, ouabain inhibition of Na efflux and K influx of rabbit RBC is easily reversible. After 2 hr, ouabain inhibition of Na efflux is completely compensated for by increased internal Na concentration and Na efflux returns to initial levels. Removal of ouabain at this stage results in stimulation of the efflux by 4.3 mmoles/kg.hr. Na influx is initially not affected by ouabain but is increased by 2.4 mmoles/kg.hr after 2 hr incubation with the drug. Removal of K from normal Ringer does not affect Na efflux and increases Na influx by 1.6 mmoles/kg.hr. Addition of ouabain to K-free Ringer inhibits Na efflux and influx to the same extent (1.6 mmoles/kg.hr). Removal of Na from K-free Ringer has an inhibitory effect on efflux similar to that of ouabain. These findings suggest that the fraction of Na efflux inhibited by removal of external K is completely replaced by a new, ouabain-sensitive exchange diffusion of Na ions.
1. Adult cats were rendered hypo- and hypernatraemic by peritoneal dialysis. These states were maintained for periods of 2-5 days.2. The concentrations in cerebrospinal fluid (c.s.f.) of the cations, potassium, calcium and magnesium all decreased in the hyponatraemic animals and increased in the hypernatraemic animals. These shifts in c.s.f. cation concentrations did not relate to plasma changes in the same cations, which were often in the opposite direction.3. The relations of the cation concentrations to c.s.f. sodium were not linear and, in the cases of calcium and magnesium, the relevant cation concentration related better to the square rather than the first power of the c.s.f. sodium concentration.4. Brain water changed much less in the hypo- and hypernatraemic animals than might be anticipated from the shifts in blood osmolarity, plasma sodium concentration and muscle water.5. Isotonicity of the fluids in brain with blood plasma and c.s.f. appeared to be largely maintained by loss or gain of sodium and chloride ions by this tissue.6. The c.s.f. results may be partly due to a constant influx of the cation in question being diluted with more formed c.s.f. in hyponatraemia and less c.s.f. in hypernatraemia, but the deviations from linearity in the plots of c.s.f. cation against c.s.f. sodium suggest the influence of other factors.