abnormalities renal function circulatory reflexes...

Abnormalities of Renal Function andCirculatory Reflexes in Primary

AldosteronismBy EDWARD G. BIGLIERI, M.D., AND MALCOLM B. MCILBOY, M.D.

IN PATIENTS with autonomic insufficiency,rapid intravenous infusion of an isotonic

solution of sodium chloride results in abnor-mally rapid renal excretion of both sodiumand water.' An identical renal response tointravenous infusion of saline solution wasobtained in a preliminary study of two pa-tients with primary aldosteronism.2 In subse-quent investigations of hyperaldosteronism ofrenal and adrenal origin,3'4 determinations ofarterial pressure during Valsalva's maneuvershowed an absence of hypertensive "over-shoot" after release of intrathoracic pressurein the group with primary aldosteronism.These observations led us to undertake a moredetailed investigation of the renal response tosalt loading and the circulatory reflex reac-tivity of the patients with adrenal adenomas.The results of studies carried out before andafter surgical removal of the tumor and ofadditional preoperative studies in three pa-tients before and after potassium repletionare described in this report.

Clinical DataThe study group consisted of nine patients with

primary aldosteronism, eight of whom have beendescribed in detail previously.4 The pertinentclinical and laboratory data are summarized intable 1. The criteria for diagnosis were thepresence of hypertension, hypokalemic alkalosis,and increased urinary excretion of aldosterone.Hypokalemia was present in all patients; twopatients had a long history of weakness and po-tassium depletion. One patient was normovolem-ic; in the other eight, total blood volume ranged

From the Department of Medicine and the Cardio-vascular Research Institute, University of CaliforniaSchool of Medicine, San Francisco, California.

Supported by grants from the National Instituteof Arthritis and Metabolic Diseases (AM-06415) andthe National Heart Institute (HE-06285), U. S. Pub-lic Health Service.

78

from 10 to 40 per cent above "predicted" nor-mal volumes calculated on the basis of heightand weight.5 Significant nocturia was a symptomof all patients. In all cases, the abnormalities dis-appeared or became less severe after surgical re-moval of an adrenocortical adenoma. A decreasein blood pressure was a consistent finding afterthe operation, although five of the nine patientsremained slightly hypertensive.

MethodsRenal studies were carried out on five of the

nine patients 4 to 8 weeks preoperatively and6 to 10 weeks postoperatively. Circulatory reflexreactivity was tested in six of the patients at ap-proximately the same intervals. In additional pre-operative studies in two cases, renal function andcirculatory reflex tests were performed beforeand after the addition of potassium chloride, 8 to12 Gm. daily, to the diet for 1 week. In theninth patient, circulatory reflex tests were carriedout before and after administration of spironolac-tone, 1 Gm. daily, for 3 days.

All hypertensive medications were discontinued3 or more weeks before the patients were studied;four of the group had never been treated forhypertension. To avoid the effect of variations insalt intake, studies were carried out after thepatient had received a diet containing 110 mEq.of sodium chloride daily for at least 1 week.The renal response to salt loading was studied

after the patient had fasted overnight. After con-trol specimens of urine had been collected viacatheter, 3 liters of sodium chloride solutionwere infused at a rate of 50 ml. per minute for60 minutes, as described previously.2 Glomerularfiltration rates were established by inulin clear-ance.6 Urinary sodium levels were determined byinternal standard flame photometry.

Circulatory reflex reactivity was studied bymeasuring the response of arterial pressure andpulse rate during a number of test conditions,according to the technic of Sharpey-Schafer.7Systemic arterial pressure was recorded contin-uously by means of a catheter inserted into abrachial artery8 and connected to a strain-gaugeheld at the levels of the sternal angle. Pulse ratewas determined from the arterial pressure tracing.Measurements of arterial pressure and pulse rate

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PRIMARY ALDOSTERONISM

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were made during a standard test procedure inthe following sequence: (1) the Valsalva ma-neuver, with mouth pressure held at 40 mm. Hgfor 10 seconds, while the patient was standing;(2) alternate 30-second periods of squattingand standing; (3) the Valsalva maneuver, as de-scribed, while the patient was lying down; (4)mental arithmetic for 30- to 60-second periods,during which the patient was successively askedto subtract either 7 or 9 from a number between90 and 100; attempts were made to hurry theanswers; (5) a "cold pressor test," consisting ofimmersing one of the patient's hands in ice-coldwater for 1 minute; (6) inhalation of amyl ni-trite (four sniffs from a freshly opened ampule);(7) continuous infusion of norepinephrine, inamounts that were increased every 2 minutes untilsystolic or diastolic pressure had risen 20 mm.Hg or more above the control value.

Control measurements were made while thepatient was recumbent and resting. Since theresults of the test procedures vary in normal sub-jects of different ages, each patient served as hisown control.

ResultsRenal Responses to Saline Infusions

Before and after operation. The results ofinfusion of isotonic saline solution in the five

patients tested are shown in figure 1 and table1. Preoperatively, the infusions resulted inprompt diuresis and natriuresis and an in-crease in glomerular filtration rate averaging52 per cent above control values. Urinary ex-cretion of sodium ranged from 2,500 to 4,500,uEq. per minute and urinary flow from 25 to40 ml. per minute. These changes reached amaximum during the last 10 to 15 minutes ofthe infusion period.

After the operation, a slight decrease incontrol inulin values was noted in four of thefive patients. The postoperative infusions ofsaline solution were followed by minimal in-creases in urinary flow and sodium excretion.The average increase in glomerular filtrationrate was only 17 per cent above control values.

Before and after potassium replacement. Inpreoperative studies on two patients beforeand after dietary addition of potassium, theresults were similar to those obtained afterthe operation. In both patients, the abnormalrenal response to saline infusions was cor-rected by administration of potassium chlor-ide (fig. 2).

Figure 1Response to intravenous infusion of isotonic sodium chloride solution in five patients with pri-mary aldosteronism before and after surgical removal of an adrenal adenoma.

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ISOTONIC NoCIINFUSION50 ml/nin

1500

1000 _URINARY SODIUM

p Eq/ rin 500

250

0

40 _

30

20

10 _URINE VOLUME

ml/irin/ Ar-

GLOMERULARFILTRATIONRATE

mI/mrirn

20 40 60 so0

TIME IN MINUTES

Figure 2

Response to intravenous infusion of isotorchloride preoperatively in two patients witaldosteronism after dietary potassium reple

Circulatory Reflex ReactivityBefore and after operation. The a

tests before and after removal of ar

adenoma are shown in figures 3 and 4 andtable 2. Preoperatively, impairment of circula-tory reflex reactivity was demonstrable in allcases. The most marked abnormalities wereshown by the two patients with hypokalemiaand weakness of long duration (cases 4 and7,? table 1). The responses obtained in thepostoperative studies showed a return to morenormal reflex reactivity. In two cases, testsrepeated 2 months after the operation showedno further changes.The representative responses to Valsalva's

maneuver in various positions in three of thesix patients tested is shown in figure 3. Pre-operatively, the hypertensive overshoot in ar-terial pressure and the reflex bradyeardiaseen normally after release of intrapulmonarypressure was minimal (four cases) or absent.Both systolic and pulse pressures decreased

40,60 during the maneuver. Since the stimulus tothe baroreceptor mechanism is greater duringstanding than during recumbency, the fall insystolic and pulse pressures was greater when

tic sodium the patient was standing than when he was

ttion. lying down. Postoperatively, the overshoot

after Valsalva's maneuver approached normal(fig. 3).

results of Changes in posture. In the five patientsi adrenal tested, preoperative arterial pressure tracings

Figure 3

Representative response to the Valsalva maneuver in three patients with primary aldosteronismbefore and after surgical removal of an adrenal adenoma.

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Figure 4Response of blood pressure and pulse rate to changesin posture in a representative patient with primary al-dosteronism before and after surgical removal of an

adrenal adenoma.

during alternate periods of squatting andstanding (fig. 4) showed no evidence of a

reflex response to the rise in pressure on squat-ting. Postoperatively, the tracings showedbradyeardia on squatting and tachycardia on

standing, as is seen in normal subjects.9The average systolic and diastolic pressures

and pulse rate in the five patients during re-

cumbency (control) and standing are com-

pared in table 2. As shown, the blood pres-

sure did not return to normal levels, eitherbefore or after the operation, while the pa-

tients were standing. Preoperatively, the aver-

age systolic and diastolic pressures duringstanding were less by 27 and 9 mm. Hg, re-

spectively, than the control values, and thepulse rate was increased an average of 11beats per minute. Postoperatively, the reflexresponses to standing were more normal. Theaverage pulse rate during standing was in-creased by 24 beats per minute, although theaverage systolic pressure was only 14 mm. Hgless than the control value and diastolic pres-

sure rose an average of 5 mm. Hg.Other tests. The response of the five patients

to all other tests also indicated impairmentof circulatory reflex reactivity preoperativelyand small but definite increases in reactivitypostoperatively (table 2). Before the opera-

tion both arterial pressure and pulse rate rose

during mental arithmetic and the cold pressortest. Because of the fall in blood pressure

after removal of the adrenal adenoma, theapplication of these stimuli in postoperativetests resulted in relatively greater rises inpressure. During inhalation of amyl nitrite,blood pressure decreased and heart rate in-

Table 2Results of Circulatory Reflex Studies in Five Patients with Primary Aldosteronism beforeand after Surgical Removal of an Adrenal Adenoma

Before operation After operationMean blood pressure Pulse Mean blood pressure Pulse

rate rateSystolic Diastolic (beats/ Systolic Diastolic (beats!

Test* (mm. Hg) min.) (mm. Hg) min.)

Control 213 105 72 163 88 84Standing 186 96 83 149 93 108

Difference -27 -9 +11 -14 +5 +24Control 202 101 72 160 95 86Mental arithmetic 219 114 80 183 109 92

Difference +17 +13 +8 +23 +14 +6Control 197 96 70 157 91 86Cold pressor test 226 115 79 191 109 96

Difference +29 +19 +9 +34 +18 +10Control 213 108 76 158 88 86Amyl nitrite inhalation 140 68 95 106 59 115

Difference -73 -40 +19 -52 -29 +29Control 205 101 73 154 91 87Norepinephrine infusiont 241 113 66 201 106 74

Difference +36 +12 -7 +47 +15 -13

*Control values were obtained while patients were recumbent and quiet.tAt a rate of 9 ytg. per minute.


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creased preoperatively. Postoperatively, thedecrease in blood pressure was less than be-fore the operation; however, the increase in

heart rate was greater. Both before and afterthe operation, infusion of norepinephrine ata rate of 9 jug. per minute was required to ,effect a rise of 20 mm. Hg or more in bloodpressure and a decrease in pulse rate. Post-operatively, infusion of the same amount of ......

norepinephrine at the same rate resulted in a

greater increase in arterial pressure and a

greater decrease in pulse rate.After potassium repletion. The results of

circulatory reflex tests carried out preoper-

atively on three patients after administration Response to

of potassium or spironolactone were similar test on a pto those obtained postoperatively. In all three, potassium r(

circulatory reflex responses showed a return tone.to near normal reactivity. The response of theblood pressure and pulse rate during thestanding Valsalva maneuver in the patient The abs(treated with spironolactone is illustrated in the Valsalfigure 5. As shown, hypertensive overshoot responses 1and bradycardia occurred only after potas- nite evidersium repletion. The results of other tests of flex activitcirculatory reflex reactivity before and after dosteronisrpotassium repletion are shown in table 3. renal func

Table 3Results of Circulatory Reflex Studies in Three Patientsbefore and after Potassium Replacement

Figure 5

>the Valsalva maneuver in a preoperativepatient with primary aldosteronism afterepletion by administration of spironolac-

Discussion,ence of hypertensive overshoot afterIva maneuver and the abnormalto changes in posture provided defi-ice of impairment of circulatory re-

ty in the patients with primary al-m. In the four cases in which both-tion and circulatory reflexes were

with Primary Aldosteronism

Test*

ControlStanding

DifferenceControlMental arithmetic

DifferenceControlCold pressor test

DifferenceControlAmyl nitrite inhalation

DifferenceControlNorepinephrine infusiont

Difference

Before replacementMean blood pressure Pulse

rateSystolic Diastolic (beats!

(mm. Hg) min.)

208 110 82

190 108 94-18 -2 +12

195 105 78205 112 82+10 +7 +4195 102 76223 122 84+28 +20 +8200 108 81128 58 103-72 -50 +22

200 105 72

222 118 67

+22 +13 -5

After replacementMean blood pressure Pulse

rateSystolic Diastolic (beats /

(mm. Hg) min.)

193182-11195213

+18190221+31193131-62192233+41

102107

+5101113+1298122+2410370

-3398116+18

7790

+137780+36886

+187496

+227268-4

*Control values were obtained while patients were recumbent and quiet.tAt a rate of 9 ,ug. per minute.

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studied, the results indicated a temporal re-lationship; the responses to salt loading andtests of reflex reactivity returned to normalor near normal at about the same time afterthe operation. Repetition of the reflex testsin two cases 2 months later showed no furtherchanges. In all cases nocturia also disappearedshortly after the operation, suggesting thatthis symptom might be related in some wayto the abnormalities of renal function and re-flex reactivity.The relationship of both the reflex and

renal abnormalities to the hypertensive stateis not clear. Several clinical and experimentalinvestigations have been concerned with cir-culatory reflex activity in hypertension. In pa-tients with essential hypertension, the responseto the cold pressor test is abnormally great.10In hypertensive rats, the reflexes involvingthe aortic and carotid baroreceptors are nor-mal."1 A normal response to the Valsalva ma-neuver was reported in two patients withsevere hypertension of renal origin and sec-ondary hyperaldosteronism;4 one of these pa-tients had hypokalemia, as well as hyper-aldosteronism and hypertension, all of whichwere present in our patients preoperatively.

In patients with essential hypertension, in-travenous infusion of saline solution is fol-lowed by increased excretion of sodium chlor-ide but no change in glomerular filtrationrate.12 Ortuizar and associates,'3 however, re-ported a decrease in the excretion of infusedsaline after administration of ganglion-block-ing agents in hypertensive patients and in onepatient with primary aldosteronism. In ourpatients, postoperative studies showed limitedexcretion of salt loads, similar to that foundin normal subjects, yet two of the five pa-tients tested were still hypertensive at thetime. In preoperative tests on our patients, therapid excretion of sodium chloride after in-fusion of saline solution appeared to be re-lated, at least in part, to increases in glomeru-lar filtration rate and filtered load of sodium,as is seen eharacteristically in patients withautonomic insufficiency.' This lability of glo-merular filtration rate and prompt excretionof infused sodium chloride solutions does not

occur in normal subjects. According to Gill,Mason, and Bartter,14 however normal sub-jects treated with ganglion-blocking agents toabolish the hypertensive overshoot followingthe Valsalva maneuver rapidly excrete suchsalt loads.

Circulatory reflex responses are also affect-ed by ganglion-blocking agents, as well as byother drugs such as reserpine, chlorothiazide,monoamine oxidase inhibitors, and certaintranquilizers.'5' 16 The effect of drugs wouldnot account for the abnormal responses in ourpatients, however, since all antihypertensivemedications were withdrawn at least 3 weeksbefore the studies; in addition, four patientshad never been treated.The impairment of circulatory reflex func-

tion in the patients with primary aldosteron-ism was not so severe as that found in tabesdorsalis,7 diabetes mellitus,17 or idiopathicpostural hypotension.18 None of the patientshad symptoms of autonomic insufficiency, withthe possible exception of nocturia, and in nocase did blood pressure fall to normal levelswith change in posture to the standing posi-tion. The failure of postural changes to pro-duce noticeable variations in blood pressuremight be related to hypervolemia, which waspresent in eight of the nine patients.

In an attempt to localize the site of the reflexabnormalities in our patients, a number oftests were used to assess circulatory reflexfunction. Both the response to central nervousstimuli, such as mental arithmetic7 and localcold,19 and the response of the aortic andcarotid baroreceptors during the Valsalva ma-neuver and postural chbanges were tested. Thegeneralized depression of response to bothtypes of test indicate that in patients with pri-mary aldosteronism the lesion does not liein the afferent pathways, as it does in tabesdorsalis and diabetes mellitus.7' 17

Interpretation of the results in our patients,however, is complicated by the fall in bloodpressure that occurred in all cases after re-moval of the adrenal adenoma. If the increaseor decrease in pressure and pulse rate duringeach test (tables 2 and 3) were expressed aspercentage changes rather than as absolute


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changes in millimeters of mercury, the re-sponses to mental arithmetic, the cold pres-sor test, and infusion of norepinephrinewould appear greater in magnitude and theresponses to postural changes and inhalationof amyl nitrite would appear smaller in mag-nitude. Expression of the results in this fash-ion, however, would not greatly alter theirsignificance. In addition, the normal range ofvariability of circulatory function is not welldefined. In three of the six patients tested, theabnormal responses became apparent onlywhen the results of the preoperative and post-operative studies were compared (table 2).The most marked abnormalities in circula-

tory reflex responses were in the two patientswho had a long history of weakness and potas-sium depletion. To our knowledge, impairmentof circulatory reflexes has not been ob-served in association with weakness and pros-tration, although both are symptoms of potas-sium depletion.20 The results obtained in threecases after potassium repletion also suggestthat hypokalemia plays an important part inthe production of both renal and circulatoryreflex abnormalities. Conflicting data, how-ever, were obtained in a study of two normalsubjects after administration of large doses ofsalt-retaining hormones for 21 days.3 Thistreatment resulted in considerable hypervol-emia, and the response to the Valsalva ma-neuver became "square wave"'21 in type; nocirculatory reflex abnormalities could be dem-onstrated, however, and the renal response tosodium chloride infusions remained normal.Similar results were obtained after potas-sium depletion had been produced in one ofthe subjects by infusion of mannitol. Theinability to produce renal and reflex abnormal-ities in these subjects may have been at-tributable to the failure to induce hyperten-sion and the mild degree and short durationof potassium depletion. In their studies ofpotassium-deficient rats, Friedman, Freed,and Rosenman22 found impaired peripheralvascular reactivity, which they attributed to afunctional defect in the peripheral arteriolesoccasioned by potassium deficit. The reversibleabnormal responses to all tests of circulatoryCirculation, Volume XXXIII, January 1966

reflex reactivity in our patients suggest a lessreactive vascular system and less effectivecardio-accelerator impulses in patients withaldosterone-secreting tumors.

It remains difficult to link the abnormali-ties of the autonomic nervous system with theobserved renal changes. The rapid excretionof sodium chloride loads is not specific to thehypertensive state associated with primary al-dosteronism, but the mechanism may bedifferent from that in hypertension from othercauses. The increase in glomerular filtrationrate was a constant finding in the patientsstudied. Restoration of more normal circulatoryreflex responses after potassium replacementpreoperatively in three patients was asso-ciated with failure to increase sodium excre-tion during rapid infusion of sodium chloride,supporting the concept that some relationshipbetween these phenomena may exist. Bothchronic potassium depletion and hypertensionappear to be necessary to effect the observedresults. The nature of the relationship be-tween the autonomic nervous system and re-nal function in primary aldosteronism, how-ever, remains obscure.

SummaryThe renal response to intravenous adminis-

tration of isotonic saline solution and circula-tory reflex reactivity was studied in nine pa-tients with primary aldosteronism before andafter surgical removal of an adrenal aden-oma. In preoperative tests, infusion of salinewas followed by abnormally rapid renal ex-cretion of sodium and water, such as occursin patients with autonomic insufficiency. Cir-culatory reflex function was also abnormal inall patients; the most severe impairment wasshown by two patients with hypokalemia andweakness of long duration. Postoperatively,both renal and circulatory reflex responsesreturned to normal or near normal. In pre-operative tests on three patients, potassiumrepletion effected a similar correction of bothrenal and circulatory reflex abnormalities.The cause of these abnormalities in patientswith primary aldosteronism is not known.Potassium depletion may be a factor, al-

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though a general disturbance of autonomiccardiovascular function cannot be excluded.

AcknowledgmentThe authors are indebted to Mary Anne Herron

for technical assistance, to Mrs. Hisaye Mochizukifor dietary management, and to Professor Peter H.Forsham, Director of the Metabolic Research Unit,University of California School of Medicine, SanFrancisco, for his continued interest and encourage-ment.

References1. WAGNER, H. N., JR.: Influence of autonomic

vasoregulatory reflexes on rate of sodium andwater excretion in man. J. Glin. Invest. 36:1319, 1957.

2. BIGLEERI, E. G., AND FORSHAM, P. H.: Studieson expanded extracellular fluid and responsesto various stimuli in primary aldosteronism.Am. J. Med. 30: 564, 1961.

3. BIGLIERI, E. G., MCILROY, M. B., NAIMARK, A.,AND FORSHAM, P. H.: Altered autonomicnervous system and renal responses inprimary aldosteronism. J. Clin. Invest. 41:1345, 1962.

4. SLATON, P. E., AND BIGLIERI, E. G.: Hyperten-sion and hyperaldosteronism of renal and ad-renal origin. Am. J. Med. 38: 324, 1965.

5. WENNESLAND, R., BROWN, E., HOPPER, J., JR.,Scorr, K. G., HODGES, J. L., JR., AND BRADLEY,B.: Experiences with radiochromium methodfor determination of red cell volume. Scandi-nav. J. Clin. & Lab. Invest. 14: 355, 1962.

6. WALSER, M., DAVIDSON, D. G., AND ORLOFF, J.:Renal clearance of alkali-stable inulin. J. Clin.Invest. 34: 1520, 1955.

7. SHARPEY-SCHAFER, E. P.: Circulatory reflexesin chronic diseases of afferent nervous system.J. Physiol. 134: 1, 1956.

8. BERNEUS, B., CARLSTEN, A., HOLMGREN, A., ANDSELDINGER, S. I.: Percutaneous catheterizationof peripheral arteries as method for bloodsampling. Scandinav. J. Clin. & Lab. Invest.6: 217, 1954.

9. SHARPEY-SCHAFER, E. P.: Effects of squattingon normal and failing circulation. Brit. M. J.1: 1072, 1956.

10. HINEs, E. A., JR., AND BROWN, G. E.: Standardtest for measuring variability of blood pres-sure: Its significance as index of prehyperten-sive state. Ann. Int. Med. 7: 209, 1933.

11. MCCUBBIN, J. W., GREEN, J. H., AND PAGE, I. H.:

BIGLIERI, McILROY

Baroceptor function in chronic renal hyper-tension. Circulation Research 4: 205, 1956.

12. BIRCHALL, R., TUTrHLL, S. W., JACOBS, W. S.,TRAUTMEN, W. J., JR., AND FINDLEY, T.: Renalexcretion of water, sodium and chloride: Com-parison of responses of hypertensive patientswith those of normal subjects, patients withspecific adrenal or pituitary defects, and nor-mal subject primed with various hornones.Circulation 7: 258, 1953.

13. ORTU'ZAR, R., CROXATTO, R., THOMSEN, P., ANDGONZALEZ, J.: Effects of acute salt load incase of primary hyperaldosteronism before andnine months after surgical cure: Comparisonwith normal subjects and patients with es-sential hypertension before and after reduc-tion of their elevated pressure with drugtreatment. J. Lab. & Clin. Med. 54: 712, 1959.

14. GILL, J. R., JR., MASON, D. T., AND BARTTER,F. C.: Adrenergic nervous system in sodiummetabolism: Effects of guanethidine and so-dium-retaining steroids in normal man. J.Clin. Invest. 43: 177, 1964.

15. KANEKO, Y., MCCUBBIN, J. W., AND PAGE, I. H.:Mechanism by which serotonin, norepineph-rine, and reserpine cause central vasomotorinhibition. Circulation Research 8: 1228, 1960.

16. BARRACLOUGH, M. A., AND SHARPEY-SCHAFER,E. P.: Hypotension from absent circulatoryreflexes: Effects of alcohol, barbiturates, psy-chotherapeutic drugs, and other mechanisms.Lancet 1: 1121, 1963.

17. SHARPEY-SCHAFER, E. P., AND TAYLOR, P. J.:Absent circulatory reflexes in diabetic neuritis.Lancet 1: 559, 1960.

18. STEAD, E. A., JR., AND EBERT, R. V.: Posturalhypotension: Disease of sympathetic nervoussystem. Arch. Int. Med. 67: 546, 1941.

19. GODDEN, J. O., ROTH, G. M., AND HINEs, E. A.,JR.: Changes in intra-arterial pressure duringimmersion of hand in ice-cold water. Circula-tion 12: 963, 1955.

20. FOURMAN, P.: Depletion of potassium induced inman with exchange resin. Clin. Sc. 13: 93,1954.

21. SHARPEY-SCHAFER, E. P.: Effects of Valsalva'smanoeuver on normal and failing circulation.Brit. M. J. 1: 693, 1955.

22. FRIEDMAN, M., FREED, S. C., AND ROSENMAN,R. H.: Effect of potassium administration on(1) peripheral vascular reactivity and (2)blood pressure of potassium-deficient rat. Cir-culation 5: 415, 1952.



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EDWARD G. BIGLIERI and MALCOLM B. MCILROYAldosteronism

Abnormalities of Renal Function and Circulatory Reflexes in Primary

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