206 1. MALONATE 



Initial Control Malonate 50 xnM % Change 



- 46 



- 90 

 + 100 



an equivalent gain of Na+ would be expected due to the inhibition of the 

 transport mechanism responsible for K+ accumulation. The effect on water 

 transport is really quite marked and greater than with some fifty other 

 inhibitors used. Mudge suggested that malonate acts by depression of 

 aerobic metabolism in general and not necessarily by a specific inhibition 

 of succinate oxidase, which at the high concentration used is quite possible. 

 The results on malonate in vivo occasionally do not correspond to the 

 in vitro experiments, nor do they always correspond to each other. The in- 

 jection of 10 millimoles/kg malonate into rats leads to a considerable diu- 

 resis which lasts for several days (Angielski et al., 1960 a). On the other 

 hand, infusion of malonate into the renal artery of a dog at a concentration 

 of 8.7 mM causes no significant change in creatine, p-aminohippurate, or Na+ 

 clearances, and produces a 15% suppression of urinary volume (Strickler 

 and Kessler, 1963). The effects in intact animals are related to acid-base 

 imbalance in addition to direct renal action, as shown by unpublished ex- 

 periments by Goldberg (1963) in which rats were water loaded and received 

 17 millimoles/kg sodium malonate with 17 ml 10% mannitol/kg, this pro- 

 ducing certain toxic symptoms (e.g., respiratory difiiculty, sluggishness, 

 and mild cyanosis). The results are summarized in the accompanying tab- 

 ulation and it is clear that a systemic acidosis was produced. A rather 



Determination Control Malonate 



Urinary flow (ml/min) 0.054 0.058 



Urinary pH 



Titratable acidity (meq/liter) 



Creatinine clearance (ml/min) 



Na+ excretion (meq/liter) 



K+ excretion (meq/liter) 



NH4+ excretion (meq/liter) 



Plasma pH 



Plasma Na+ (meq/liter) 



Plasma K+ (meq/liter) 



