Although it is generally accepted that organic mercurial diuretics depress the renal tubular absorption of sodium,2 precise localization of their site of action within the tubule has not been accomplished. If one administers graded doses of such diuretics to the dog it becomes apparent that, above a certain level, further increases in dosage yield progressively diminishing increments of sodium excretion. This pattern of response suggests that these agents depress some specific fraction of total sodium absorption, and that this fraction might be quantitated and the mechanism itself thereby identified by the administration of doses of mercurial diuretics sufficient to block it completely.The micropuncture studies of administered, they may well act on the distal tubule. This latter conclusion, in contrast to the first, is not incontestable. It is, of course, possible that there might be two or more distinct mechanisms for sodium absorption in the proximal tubule, only one of which is mercury sensitive. That mechanism might account for 16 to 33% of the total of 67 to 87%o of filtered sodium normally absorbed in the proximal tubule. Since no evidence of functional differentiation of sodium absorption in this segment exists, we incline to the former and simpler interpretation. Our findings demonstrate (a) that there is a specific mechanism for sodium absorption which can be completely blocked by large doses of mercurial diuretics; and (b) because it accounts for 17.1 to 21.4%o of total absorption, this mechanism probably resides in the distal tubule. METHODSExperiments were performed on trained, unanesthetized dogs. Animals were used in the fasting state, at intervals of not less than one week. Glomerular filtration rate was measured by the creatinine clearance and sodium was determined in plasma and urine with an internal standard flame photometer. Other methods have been described in previous communications (3). RESULTSThe unprepared, normally hydrated dog 3 is not suitable for this study. Presumably the loss of excessive quantities of sodium and water in the urine or the cardiac and vascular toxicity of the diuretic per se so compromises circulatory function that the animal cannot for long maintain a stable renal hemodynamic state. Consistently, the onset of diuresis is followed shortly by a fall in glomerular filtration rate such that the ap-

Potential-energy surfaces have been calculated over the full range of nuclear configurations for the C1+ C12 reaction using the DIM (diatomics-in-molecules) method with the 28 polyatomic basis functions of 2A' symmetry and the 26 of 2A" symmetry arising from three Cl(*P,) atoms. The lowest 2A' surface has its lowest potential-energy barrier Eb = 28 kJ mol-' in a configuration bent by ca. 35" from the collinear configuration with 'xi symmetry. The lowest 2A" surface has its lowest barrier Eb == 75 kJ mol-I in the collinear configuration with 211u symmetry. Comparison with previous calculations on the F + F2 reaction shows that the barrier heights are lower and the bent configuration more energetically favoured over the collinear configuration on the 2A' surface, in accord with Walsh molecular-orbital theory. However, the predicted increase in bending of the 2A' transition state for C13 compared with F3 is observed to only a small extent (ca. 5")

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According to Merrill (1) and Mokotoff, Ross and Leiter (2), renal plasma flow and glomerular filtration rate are characteristically low in congestive heart failure. These investigators infer that a reduction in the rate of delivery of sodium, chloride, and bicarbonate ions into tubules having essentially normal reabsorptive capacities favors retention of electrolyte and water. In line with this concept Weston and Escher (3) observed that patients who fail to exhibit a satisfactory diuretic response to intravenous mercurials often have exceptionally low filtration rates, and that the administration of aminophylline, which increases filtration rate, greatly enhances the diuresis.Others including Seymour (4), Briggs (5), and Sinclair-Smith (6) have expressed doubt that a reduction in filtration rate is either a constant or a significant finding in congestive failure, and have observed loss of edema without any accompanying increase in filtration rate or renal blood flow.The difficulties in a clinical analysis of the role of reduced filtration rate in the pathogenesis of edema are evident. Chronic renal disease is often associated with congestive failure, and reduced filtration rate might in any given instance be more related to the former than to the latter. Furthermore, compensation is usually reestablished slowly and recovery of capacity to excrete salt and water might be more a function of readjustment of tubular absorptive capacity than of increased delivery of filtrate into the tubules. The present study on the dog was initiated with the view of establishing whether or not true glomerulo-tubular imbalance with relative overabsorption of water and salt could be induced by a reduction in glomerular filtration rate independent of changes in tubular 1 Aided by a grant from the National Heart Institute of the National Institutes of Health. function. Likewise it was hoped to determine whether a reduction in filtration rate would reduce the effectiveness of mercurial diuretics.It has been found that a relatively minor (25%) reduction in glomerular filtration rate very seriously impairs the capacity of the dog to excrete a given load of water and electrolyte both under normal conditions and following mercurial diuretics. We infer from these experiments that insofar as filtration rate is reduced in congestive failure, this factor contributes to the incapacity of the individual to maintain fluid and electrolyte balance, and furthermore limits the efficacy of the commonly used mercurial diuretics. However, we recognize that such factors as increased venous pressure (7) and overactivity of pituitary and adrenal cortical water and salt conserving mechanisms (8, 9) may well play highly significant roles in the pathogenesis of edema and in the development of clinical mercurial resistance. No attempt has been made in this study to assess clinically the relative roles played by these several factors. We merely feel that we have demonstrated the fact that a reduction in filtration rate causes glomerulo-tubular imbalance, and th...

Potential-energy surfaces have been calculated over the full range of nuclear configurations for the F + F2 reaction using the DIM (diatomics-in-molecules) method with the 28 polyatomic basis functions of 2A' symmetry and the 26 of 2A" symmetry arising from three F(2Pu) atoms.The lowest 2A' surface has its lowest potential-energy barrier Eb = 72 kJ mol-' in a configuration bent by ca. 30 O from the collinear configuration with 'Zg symmetry. The lowest 2A" surface has its lowest barrier Eb== 108 kJ mol-' in the collinear configuration with 'nu symmetry. The lowest 2A" surface shows a stronger preference for the collinear configuration than does the lowest 2A' surface, in accordance with the predictions of Walsh rnolecular-orbital theory.