THE CONTROL OF RENAL BLOOD FLOW AND GLOMERULAR FILTRATION IN NORMAL MAN Herbert Chasis, … , William Goldring, Homer W. Smith J Clin Invest. 1938;17(5):683-697. https://doi.org/10.1172/JCI100996. Research Article Find the latest version: https://jci.me/100996/pdf THE CONTROL OF RENAL BLOOD FLOW AND GLOMERULAR FILTRATION IN NORMAL MAN BY HERBERT CHASIS, HILMERT A. RANGES, WILLIAM GOLDRING AND HOMER W. SMITH (From the Departments of Physiology and Medicine, New York University College of Medicine, and the Third (New York University) Medical Division of Bellevue Hospital, New York City) (Received for publication June 7, 1938) This report is concerned with the effective renal plotted logarithmically, a convenient mode of ex- blood flow and rate of glomerular filtration in nor- pression since an equal variation up or down in mal man, as determined by the diodrast and inulin any one of the variables represents an equal per- clearances (26) during diuresis and during the centage change. Blood pressure (BP) was taken action of phlorizin, adrenin, caffeine, nitrite, and sphygmomanometrically. During acute phases of typhoid vaccine. The observations not only throw circulatory disturbance, the blood pressure was light on the action of these agents, but also af- observed every two to three minutes, and at other ford information concerning the physiological times at intervals of five to ten minutes. The fig- control of renal blood flow and glomerular activity. ures are recorded in mm. Hg. The rate of urine Typical data are reported graphically. On the flow, V, is given in cc. per minute. assumption that the diodrast plasma clearance (in- Inulin, diodrast, and phenol red were given by dicated by D in the figures) is a complete clear- constant intravenous infusion. The priming in- ance, this value is taken as equal to the effective fusion consisted of 12 grams of inulin, 1.5 cc. of renal plasma flow, i.e., the flow of plasma to active 10 per cent phenol red, and 1.5 cc. of 35 per cent excretory tissue. To convert this figure to the diodrast solution in 100 cc. of 0.85 per cent saline, effective whole blood flow it is only necessary to given at the rate of 10 cc. per minute. The sus- divide it by the per cent of plasma in the blood. taining infusion consisted of 45 grams of inulin, For brevity, the term " effective " will be omitted 10 cc. of phenol red, and 12 cc. of diodrast in from the discussion without, however, neglecting 1000 cc. of saline, given at the rate of 4 cc. per the physiological distinction between the diodrast minute. All details of technique were the same clearance and the actual plasma flow which must as those reported in the general description of be somewhat larger than the former in conse- methods given elsewhere (26). quence of the inclusion of inert tissue. The fil- tration rate has been measured by the inulin clear- Water diuresis ance (IN). The filtration fraction (FF) (i.e., Figure 1 (Subject B. L., 1.83 sq. m., 52 per cent the apparent fraction of the plasma cleared plasma) presents observations on the plasma flow through the glomeruli) is given directly by the and filtration rate during water diuresis in man. inulin/diodrast clearance ratio. The phenol red After three control periods, water was adminis- clearance (PR) has been followed in all observa- tered in four 250 cc. portions at five-minute in- tions, the data immediately above the phenol red tervals in order to minimize any disturbance of clearance in the figures being the corresponding the systemic circulation. The urine flow, shown phenol red/diodrast clearance ratio. (For the graphically, rose from 1.8 cc. to 14.2 cc. per min- significance of this ratio see the discussion of the ute. There was no change in the rate of glo- action of phlorizin.) This ratio has not been merular filtration. The plasma flow decreased corrected for the depression of the phenol red slightly, but there is no reason to believe that this clearance by diodrast, which was present in the circumstance was a result of the administration plasma in concentrations of 0.6 to 1.5 mgm. per of water, or that it was causally related to the in- cent. D, PR, and IN are expressed as cc. per 1.73 duction of diuresis. These observations are con- sq. m. per minute. These data and FF are sonant with the evidence, which has been fully re- 683 684 H. CHASIS, H. A. RANGES, W. GOLDRING AND H. W. SMITH FIG. 1 Data on Subject B. L. viewed elsewhere, that water diuresis is entirely ing evidence to the contrary, the diuresis could referable to diminished tubular reabsorption and well be attributed to a decreased excretion of the does not involve a change in renal blood flow or antidiuretic hormone, perhaps inf consequence of filtration rate (25). a centripetal stimulus from the gastro-intestinal tract. Oil of juniper Figures 1 and 2 afford two series of control (Figure 2, Subject R. D., 1.8 sq. m., 64 per observations which, with numerous other instances cent plasma.) This and other essential oils once that might be cited, warrant the conclusion that enjoyed a vogue as diuretics (1) and our exam- under basal conditions the plasma flow, filtration ination was made with this fact in mind. In one rate, and filtration fraction remain quite constant instance, 0.2 cc. of oil of juniper was given orally, under continuous observation. with no striking effect upon renal function except for a transient diuresis (2.3 to 6.3 cc. per minute). Phlorizin In the observations recorded in Figure 2 one cc. (Figure 3, Subject J. C., 1.73 sq. m., 58 per of oil of juniper increased the urine flow from cent plasma.) This glucoside produces incon- 1.5 to 8.4 cc. (In this and subsequent figures stant but sometimes marked reductions in glo- the urine flow is recorded numerically at the bot- merular activity in all animals, and blocks the tom of the graph.) It is doubtful if the increase tubular reabsorption of glucose, xylose, and su- in plasma flow is physiologically signilficant, and crose, and the tubular excretion of creatine and the filtration rate and filtration fraction remained creatinine (25). Shannon (24) reported no re- practically unchanged. In the absence of convinc- duction of the phenol red/inulin clearance ratio RENAL BLOOD FLOW AND GLOMERULAR FILTRATION 685 ........i- J' mlllu 1111MM IZZI&M-111 Iiiiui 700 s_G65~~~~~~6a§5 N70. 6 utli~~~~~~. 500WE- I --am LLI IL2 '3001- 2001 I 15I IN-1Lj llllllQTTlrT-rlrTTA&&AuWlWWI----- VS-....&.& 100 .W-U-jfTIJTIJiiiUIjI 'I1- 0. 140t 60 BP 0 C I JUNIPER IN CC. 25 PER CENT ALCOHt PEROS 7.8 84 8.3 4.0 3.3 3.8 I . 54 V L4 L2 I a t5 a I rir I CeUef-S 4'A^ coAZ^ 50In^ MINUTES 120.-A-l- 140a A ^ 160I An ^" 1OUa 91^ FIG. 2 Data on Subject R. D. in the phlorizinized dog, but Pitts' data (18) sug- larly modify the extraction ratio of diodrast, and gest that the drug may have some action on the thus invalidate the clearance method of following tubular excretion of phenol red in the chicken. the renal blood flow. This point is of such im- Our present observations demonstrate that, in portance that it requires full discussion before man, phlorizin reduces the phenol red clearance to applying this method further. a much greater extent than the diodrast clearance, The data of Table II of our previous paper the excess reduction of the phenol red clearance (26) gave the phenol red/diodrast clearance ratio being indicated in Figure 3 by the cross-hatched in 6 normal subjects as 0.56. Further data now area. This fact indicates that the drug interferes available on 10 additional subjects leave this aver- with the tubular excretion of phenol red, and pos- age at this figure, with the extreme variations of sibly also of diodrast. Since any clearance is ac- 0.46 to 0.73. In general, the ratio is very con- ceptable as an index of renal plasma flow only so stant in any one subject, as shown in Figures 1 long as the renal A-V extraction ratio remains and 2, but there is a tendency for the ratio to fall when the diodrast constant, or very nearly so, it follows that the clearance (plasma flow) is high, and to rise when the diodrast clearance is administration of phlorizin invalidates the use of low. This same inverse relation is evident in in- the phenol red clearance, and throws grave sus- dividuals in whom renal ischemial or hyperemia picion on the use of the diodrast clearance for this 1 purpose. The action of phlorizin raises the ques- The term, "renal ischemia," is used here to denote any decrease in renal blood flow below normal, in line of whether other reactive tion physiologically sub- with the use of the term, " renal hyperemia," to denote stances (adrenin, theophylline, etc.) may not simi- any increase above normal. 686 H. CHASIS, H. A. RANGES, W. GOLDRING AND H. W. SMITH FIG. 3 Data on Subject J. C. has been induced artificially. A further analysis consequence of a reduction in diffusion gradient of this phenomenon will be made subsequently, but by protein-binding, or insofar as the ratio is re- an inverse relation between the phenol red/dio- duced by temporal delay in the process of tubular drast clearance ratio and the plasma flow is to be excretion, prolongation of the renal circulation expected in theory for two reasons.