928 7. MERCURIALS 



The results obtained on kidney slices are generally in agreement that, 

 although respiration may be reduced by reasonably high concentrations 

 of mercurials (0.25-1 mM), the inhibition of various transports is much 

 greater. Thus Cross and Taggart (1950) found that 1 mM Hg++ depresses Og 

 uptake of rabbit kidney slices 35% while inhibiting p-aminohippurate ac- 

 cumulation 89%, and Mudge (1951) showed that respiration is scarcely af- 

 fected by Hg++ at concentrations markedly altering Na+ and K+ transport. 

 Mendelsohn (1955) confirmed that Hg++ can reduce p-aminohippurate ac- 

 cumulation as much as 70% without affecting respiration in kidney slices. 

 Kobinson (1956) believed that the inhibition of respiration by mercapto- 

 merin might be the basis for the swelling of rat kidney slices and the inter- 

 ference with water transport, but there was no direct evidence for a relation- 

 ship. Maizels and Remington (1958) also observed moderate respiratory 

 inhibition with mercaptomerin and meralluride, but did not feel that this 

 was the chief factor in the increase in water and Na+ of the slices. Further- 

 more, the lowest concentration of the mercurials which exerts an effect in 

 vitro is much greater than the maximal tolerated plasma concentration in 

 rats in vivo, so it is doubtful if these inhibitions of respiration are relevant 

 to the diuretic action. 



Summarizing all the data obtained on enzyme and metabolic inhibition 

 in the kidney, it is disappointing that no system particularly sensitive to 

 the mercurials has been found, and that no correlation between inhition 

 and transport processes has been demonstrated. If the basis of mercurial 

 diuresis is metabolic, no clear evidence for this has yet been provided. 



Accumulation and Excretion of Mercurials by the Kidneys 



All mercurials are rather slowly accumulated by the kidneys and the high 

 levels are sustained for periods of several days. The kidney/plasma ratio is 

 maximally around 1000 in the rat and dog when chlormerodrin is given 

 (Borghgraef and Pitts, 1956; Giebisch and Dorman, 1958), but these ratios 

 are reached only after many hours, and are in part due to the retention by 

 the kidney with falling plasma levels. The correlation between distribution 

 and excretion of a mercurial and the diuresis is well shown in the results of 

 Borghgraef et al. (1956) (Fig. 7-44). The loss of mercurial from the plasma 

 is divided into three components: that excreted in the urine, that entering 

 the various tissues, and that accumulated by the kidneys. Some mercurials 

 are excreted fairly rapidly and others slowly; meralluride administered in- 

 tramuscularly in man is 50% excreted in 3 hr (Burch et al., 1950) but 

 chlormerodrin given by the same route to rats is only 21% excreted after 

 24 hr, 67% remaining in the kidneys (Borghgraef and Pitts, 1956). We have 

 discussed the theories of the excretory mechanisms (page 923) and the 

 possible role of tubular secretion. The mercurials are not excreted entirely 

 in the form administered. Some may be split into inorganic Hg++ but most 



