EFFECTS ON THE KIDNEY 919 



are primarily natriuretics, and that the resorption of Cl~ and water by the 

 proximal tubules follows the movement of Na+ for electrostatic and osmotic 

 reasons. The evidence for the proximal site of action of the mercurials will 

 be presented later (page 920). The fundamental mechanism of action must 

 therefore be sought in the modifications of active Na+ transport by the 

 mercurials. 



(D) The mercurials can also act elsewhere on the nephron to modify urine 

 composition and flow rate. Sufficient evidence has been accumulated to show 

 that the mercurials can exert minor effects throughout the nephron — on 

 the loop of Henle, the distal tubule, and the collecting duct — to further 

 alter the urine volume, and that transport processes and exchange reac- 

 tions of various types can be inhibited. That is, the primary site of action 

 may be on active Na+ transport in the proximal tubules, but this is by no 

 means the sole site of action. The transports of a variety of substances, in- 

 cluding K+, Ca++, urate, p-aminohippurate, amino acids, and various dyes, 

 are depressed by the mercurials. 



(E) Only a relatively small effect on Na+ resorption need be exerted to pro- 

 duce marked diuresis. Inasmuch as 98-99% of the filtered Na+, CI", and 

 water is resorbed, it is evident that a reduction of this to 90-95% would 

 cause up to a 10 fold increase in excretion rate. Consequently one might 

 predict that only a small metabolic disturbance by the mercurials would be 

 necessary for diuretic action, and that so small an effect might be difficult 

 to detect under the usual conditions. Furthermore, only 15-30% of the 

 total NaCl resorption can be inhibited by the mercurials, the remainder 

 presumably being mediated through mercurial-resistant systems (Pitts, 

 1958). 



(F) The selective action of the mercurials on the kidney is mainly a conse- 

 quence of the accumulation of mercurial. Mercurials exert demonstrable ef- 

 fects only on the kidneys over a dosage range, and this is primarily due to 

 the relatively high concentrations of mercurial reached in the renal tissue, 

 whether this is achieved by tubular secretion or filtrate resorption (page 

 928). The transport systems are probably no more sensitive than in other 

 tissues to the mercurials (at least there seems to be no clear evidence for 

 this). However, the point mentioned in the previous paragraph that only 

 small effects on renal transport need be exerted may be a factor in increas- 

 ing the apparent sensitivity of the kidney. 



(G) The reported renal responses to the mercurials are quite variable. One 

 cannot fail to be impressed by the general lack of agreement on certain 

 basic actions of the mercurials despite the great amount of work done over 

 many years, and it is disturbing that almost every hypothesis can be re- 

 futed by evidence of apparent validity. It may be helpful to list some of the 

 reasons for these disagreements. (1) Work done with different species can 



