Electrolyte excretion patterns due to chlorothiazide, a new orally effective diuretic agent

Southern Society for Clinical Research change in plasma volume. Acute reduction of arterial pressure in twenty-one pregnant or postpartum patients in an acute hypertensive state was accompanied by varying responses in plasma volume which were unrelated to changes in cardiac output, mean circulation time or central blood volume. 1. A 33 per cent average reduction in arterial pressure in six patients more than two weeks before or after delivery was accompanied by an average increase of plasma volume of 29 5 8 per cent. 2. A 34 per cent average reduction in arterial pressure in fifteen patients less than two weeks before or after delivery was accompanied by an 11 + 10 per cent average decrease in plasma volume. The reproducibility of these divergent responses of plasma volume following reduction of arterial pressure in the same patients at different periods of pregnancy suggests that proximity to delivery changes the body’s reaction to the acute hypertensive state. ELECTROLYTE CHLOROTHIAZIDE,

EXCRETION A

NEW

PATTERNS ORALLY

DUE

TO

EFFECTIVE

DIURETIC AGENT. Ralph V. Ford and Charles L. Spurr. V. A. Hospital, and the Dept. of Medicine and Pharmacology, Baylor Univ. College of Medicine, Houston, Texas.

The electrolyte excretion patterns in ten human subjects given chlorothiazide, 6-chloro-7sulfamyl-1,2,4-benzothiadiazine-l,l-dioxide have been observed in six fractional periods per twenty-four hours. Six incremental amounts (31.75 mg. to 1000 mg.) as a single dose on two consecutive days were repeated ten times to achieve statistical significance. There was a oneto threefold increased sodium excretion per twenty-four hours, depending upon the dose. The greatest increase (three- to fivefold) appeared in the second two-hour period. Increased potassium excretion paralleled but did not equal sodium excretion. Chioride excretion paralleled sodium excretion, but appeared to be greater after the first six hours, while bicarbonate excretion was most marked and the pH highest during the first six-hour period. Ammonia excretion was depressed during the phase of greatest natriuresis. Titratable acidity increased during the last twelve hours following drug administration and was especially marked during the first post-drug day. Thus in its initial effects this non-mercurial diuretic agent appears to have properties similar to those of the carbonic anhydrase inhibitors, JUNE,

1957

in its later effects and resembles those of the mercurial diuretic agents. At the doses tested its potency appears to be roughly equal to or greater than orally administered chlormerodrin (neohydrin@) . RELATIONSHIP

BETWEEN

TRANSCAPILLARY

MOLECULAR

EXCHANGE

IN

SIZE

AND

HUMAN

THE

Edward D. Freis, Frank A. Porjido, Harold W. Schnaper and Renato D. Kouach. Dept. of Medicine, Georgetown Univ. Hospital, and V. A. Hospital, Washington, D. C. FOREARM.

Using methods previously described (Proc. Sot. Exper. Biol. & Med., 92: 188, 19563 for measuring the transcapillary exchange of labeled substances a study was carried out of the relationship between the “permeability” of various substances and their molecular size. The per cent transcapillary losses (means of four or more cases) and effective molecular volumes for four labeled substances were as follows: Rba6, 76 per cent loss, mol. size 11.8 (A0)3 per ion; S35-labeled L-methionine 48 per cent loss, 156 (A’)” per molecule; S35-labeled glutathione 39 per cent loss, 352 (A”)3 per mol. and I’“‘-labeled diiodotyrosine 29 per cent loss and 278 (A”)” per mol. These data indicate an approximate correlation with molecular size. The relationship is strengthened by the additional observations that the per cent losses of D20 at peak concentrations of the dye curve averaged 90 per cent and that inulin (a large molecule) exhibited transcapillary losses averaging 21 per cent. These data are consistent with the concept of restricted diffusion. The transcapillary losses of substances of small molecular size were too great to be explained on the basis of filtration alone. However, as molecular size increased the trend was toward a progressive decrease in transcapillary exchange. SERUM IN

LIPOPROTEINS,

INSTITUTIONALIZED

GLYCOPROTEINS EUNUCHS

AND 4ND

LIPIDS

NON-CAS-

TRATE MALE SUBJECTS. R. H. Furman, R. P. Howard, M. R. Shetlar and R. Imagawa. C#ardiovascular and Endocrinology and Metabolism Sections, Oklahoma Medical Research Foundaof Medicine and Biochemistry, tion, Dept. Univ. of Oklahoma School of Medicine, and the Research Laboratory, V. A. Hospital, Oklahoma City, Okla.

Eunuchs manifest less coronary atheroscIerosis than non-castrate men. This prompted a study of twenty-four eunuchs and twenty non-castrate