EFFECTS ON THE KIDNEY 933 



Moyer et al. (1957) and Handley and Seibert (1956) could detect no inor- 

 ganic mercury after administration of meralluride, but Weiner et al. (1962) 

 pointed out that Hg++ would be excreted mainly as the cysteine complex 

 and this would be included with the organic mercurial in their chromato- 

 graphic fractionations. It is also possible that very tight binding of the ac- 

 tive Hg++ in the kidney would occur, so that the excretion would be slow. 

 Weiner et al. (1962) could detect Hg-cysteine in the urine following injec- 

 tion of 3 particularly labile mercurials, but of course this is not valid evi- 

 dence that the Hg++ is the active form. 



Clinical diuretic refractoriness to the mercurials has been known for years 

 and it is often possible to restore the diuretic response by giving NH4CI. 

 The potentiating action of NH4CI has been the subject of much work and 

 speculation, but the mechanism is still unknown. One hypothesis is that 

 the urinary acidification is the major factor. Weiner et al. (1962) assume 

 that this acidification increases the splitting of the labile mercurials. Ad- 

 ministration of NH4CI drops the pH of the urine below 5 and an optimal 

 effect is usually seen around 4.5; thus the splitting of the mercurial in the 

 urine will be significantly accelerated. However, the Hg++ in the urine wiU 

 presumably be complexed with cysteine or other simple thiols and the rate 

 of splitting will not be very great. It has also generally been assumed that 

 the splitting occurs in the tubular cells. Although the intracellular pH un- 

 doubtedly falls after NH4CI, the decrease is certainly not as great as in 

 the urine. Pending determinations of intracellular changes, one cannot esti- 

 mate the effect this would have on mercurial splitting. The mercury con- 

 tents of the proximal tubules in the dog were determined histochemically 

 by Cafruny (1962), using di-/?-naphthylthiocarbazone, and acidosis was 

 shown to increase the levels for chlormerodrin and Hg++, although a de- 

 crease occurs with p-MB. He felt that acidosis either increases the available 

 receptors for mercurials or somehow alters the affinity of the mercurial for 

 the receptors. Change in the acid-base balance does not alter the excretion 

 of the mercurials, so it is presumably not a matter of the tubular concen- 

 tration of mercurial. If the fall in pH is responsible for increased splitting 

 of the mercurials and thus a greater diuretic effect, NH4CI administration 

 or other acid-base changes should not affect the diuresis produced by Hg++ 

 complexes. Mudge and Weiner (1958) and Levy et al. (1958) reported that 

 the action of meralluride is altered more than Hg-cysteine by variations in 

 the urinary pH. However, Hg-cysteine diuresis is increased 2.4-fold in go- 

 ing from alkalosis to acidosis, so that the results are not as clear-cut as one 

 might wish. If acidosis is responsible for greater mercurial action, one 

 would also expect that any type of acidosis would be effective. However, 

 Kessler (1960) points out that inhalation of 12% CO., actually decreases 

 mercurial diuresis, although not as much as alkalosis produced by HCOg" 

 infusion. But inhalation of 12% CO2, although it produces an acidification 



