Noradrenaline Release and Metabolism in

Orthostatic (Postural) HypotensionBy McC. GOODALL, M.D., PH.D., W. R. HARLAN, JR., M.D., AND H. ALTON, B.S.

SUMMARYFifteen hypotensive patients were studied of whom only seven could be classified

as having idiopathic orthostatic (postural) hypotension. These seven patients showeda marked decrease in their urinary output of the sympathetic neurohormone, noradren-aline. Furthermore, the rate of metabolism of circulating noradrenaline was

somewhat less than normal; however, there was no significant alteration in nora-

drenaline metabolites. One patient, on whom autopsy was performed, showeddegeneration of the sympathetic ganglia and nerves. Although there was infiltration withamyloid in these areas, it was not certain that amyloidosis was the primary disease.Nevertheless, there was an anatomic loss of the neurogenic structures involved in thesynthesis of noradrenaline, which could explain the subnormal output of noradrenaline.Whereas, these results do not permit a definite conclusion that in idiopathic orthostatichypotension there is an anatomic deficit or a decrease in efferent sympathetic neurons,

nevertheless, evidence is presented which would seem to indicate this as the probableetiology.

Additional Indexing Words:Sympathetic neuron degenerationAmyloidosis Adrenaline Norepinephrine

Urinary output of noradrenalineScintillation studies

SINCE the description of orthostatic hypo-tension by Bradbury and Eggleston'

many reports2-11 and several reviews12-14have been published on this subject. Thecauses of orthostatic hypotension are numer-ous; many are related to other diseases suchas diabetes mellitus and neurological diseases,but particularly perplexing has been thatgroup of patients having orthostatic hypoten-sion without apparent underlying cause. Inthese patients there is functional alteration inthe sympathetic nervous system that is mani-fested by inadequate arteriolar constriction,anhidrosis, sexual impotence, fixed heart rate,and often loss of bladder function, and diar-rhea; the latter is probably related to para-

From the Departments of Surgery and Physiology,The University of Texas Medical Branch, Galveston,Texas, and the Department of Medicine, MedicalCollege of Virginia, Richmond, Virginia.

Dr. Harlan is a Markle Scholar in Academic Medi-cine.

This investigation was supported by Grant HE-11294 from the U.S. Public Health Service.

Circulation, Volume XXXVI, October 1967

sympathetic dysfunction. Although many in-vestigators6' 11, 12, 14 have suggested that thesympathetic nervous system was involved inthe pathogenesis, the experiments by Luftand von Eulerl were the first to demonstratea decreased release of the sympathetic neu-rohormone, noradrenaline (norepinephrine).Later, Barnett and associates,'6 Hickler andco-workers,'7 and Sundin13 showed similarchanges in orthostatic hypotension, and Good-all and associates18 related the hypotension re-sulting from wightlessness to decreased sym-pathetic nerve activity.The pathogenesis of the decreased norad-

renaline output remains obscure. However,such decrease could result from a defect inthe biosynthesis of noradrenaline, a decreasein its release, or an aberration in noradrenal-ine metabolism. The purpose of these experi-ments was to evaluate orthostatic hypoten-sion in terms of release and metabolism ofthe sympathetic neurohormone.

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MethodsFifteen hypotensive patients were studied. Of

this number, only seven could be classified ashaving idiopathic orthostatic (postural) hypoten-sion. The other eight did not fall into this cate-gory since they had either an associated diseaseof the nervous system, that is, diabetic neurop-athy, tabes, or syringomyelia, or had otherknown causes for their hypotension unrelated tothe nervous system.Some of the patients were studied at the Clin-

ical Research Center, Medical College of Vir-ginia (FR 0065), and others were studied intheir local hospitals. Each patient remained atsedentary activity or rest in bed. All medicationswere discontinued for at least 2 days prior tothis study. Renal function of each patient wasevaluated and found to be normal. Table 1 is asummary of the clinical findings of each pa-tient with orthostatic hypotension in whom themetabolism of noradrenaline was studied.

Bioassay of Urine for Noradrenaline

One or more 24-hour urine samples were ob-tained from each of the patients and bioassayedfor noradrenaline and adrenaline. The bioassay,although less sensitive than most fluorometricmethods, was used in these experiments becauseof its specificity; it measures the biological activ-ity of the natural-occurring isomers of noradrenal-ine and adrenaline.

Preparation of the urine extract was in ac-cordance with the procedure adopted from vonEuler and Hellner'9 and has been used by otherinvestigators.18' 20 In brief, the urine was hy-drolyzed and the adrenaline and noradrenalinewere selectively adsorbed on aluminum hydrox-

TableClinical Findings in the Five Patients with Orthostaticvenous Injections of Noradrenaline 2-14C

ide and filtered. The precipitate was washed andredissolved with 2 N H2SO4. The remaining saltswere precipitated by mixing the extract withalcohol-acetone and filtered. The filtrate whichcontained the adrenaline and noradrenalinewas concentrated in vacuo and tested on thecat's blood pressure which is sensitive to noradren-aline and on the hen's rectal cecum which is sen-sitive to adrenaline. Having determined the ac-tivity ratio for adrenaline and noradrenaline onthe cat's blood pressure and on the hen's rectalcecum and the activity of the patient's urinaryextract in terms of l-noradrenaline, the relativeamounts of adrenaline and noradrenaline in theurine were calculated.'19 20

Metabolism of NoradrenalineFive of the seven subjects who had idiopathic

orthostatic hypotension were given 9.5 luc (80ugg) of dl-noradrenaline 2-14C* (S.A. 20 mc/mmole) (table 1) . The purity of the injecteddose as determined by column and paper chroma-tography was found to be at least 95%. Thelabeled noradrenaline was mixed with 10 ml ofdistilled water and injected into the antecubitalvein over a period of 1 minute. Urine was col-lected by means of an indwelling catheter(Foley) at 10-minute intervals for 70 minutes,hourly for the next 5 hours, and a singl.e collec-tion was made during the subsequent 18 hoursfor a total of 24 hours. The urine specimenswere immediately frozen and stored at -20 C un-til assayed.

Procedures for the separation and quantitationof the urinary catabolites of noradrenaline and

*Volk-Radio-Chemical Company, Chicago, Illinois.

1Hypotension Who Were Sttudied Following Intra-

AgePatient (yr)

Durationof

symptomsSex (yr)

Blood pressure Bladder or(mm Hg) Sexual bowel

Supine Standing Anhidrosis impotence symptoms

52 M 5 148/84 40/2027 M 8 120/84 60/0

E.O.M. 50 F 14 140/72 0/0

44 F 10 180/80 80/5046 M 3 118/70 0/0

+ + + Chest pain with lowblood pressure

+ - + Motor and sensory

nerves diminished inright leg

-4-

+ + Delayed nerve conduc-tion in lower extremities

*All patients had normal carbohydrate tolerance, normal urinary 17-hydroxy- and 17-keto-steroids, and normalrenal function.

tPatient died later. Significant findings at necropsy included degeneration of sympathetic ganglia and replace-ment with amyloid.

Circulation, Volume XXXVI, October 1967

L.W.L.S.

I.Z.M.Q.t

Otherfindings*

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Figure 1

Section of symiipathetic nerve. Deposits of amnyloid acre present within the nerve cauising dis-ruption anid replacement of nerve fibers. Heizatoxylil and eosin, X 220.

adrenalinle in normal subjects have been pre-viously described.2 22 In brief, an aliquot ofurine containing 100,000 to 150,000 dpm wasplaced on a 1 x 5 cm column of Amberlite IRC-50 resin.* The column was washed with 30 ml ofwater. The effluent and wash were combined andsaved. The Amberlite column was then elutedwith 40 ml of 0.5 N acetic acid.The column effluent (wash) anid eluate were

each assayed for total radlioactivity as follows. In-to each of two 20-ml counting vials xvas placed1.0 ml of sample, to which was added 15.0 mlof previously prepared liquid fluor containing 15g of naphthalene, 50 mg of POPOP, 2 g of PPO,500 ml of absolute ethaniol, and 500 ml of re-agent toluene. This was counted for 20 min-utes, using a Packard automatic liquid scintilla-tion spectrometer.An aliquot of the eluate, containing 500 dpm,

was evaporated to abouit I ml and cbromato-

*CG-50, type II, Rohn & Hass Co., Philadelphia,Pennsylvania.Crculation, Volumze XXXVI, October 1967

graphed for 24 hours on Whatman no. 1 paper;n-butanol saturated with N HCL was used as thesolvent. After drying, the paper was cut into 1-cm strips. Each strip was placed in a 20-ml count-ing vial filled with scintillation liquid, and itsradioactivity was measured with a Tri-CarbLiquid Scintillation Spectrometer. Three radioac-tive peaks were obtained, corresponding to nor-adrenialine, normetadrenaline, and an unknowncompound. Tbe percentage of radioactive nor-adrenaline, normetadrenaline, and the unknownsubstance in each sample was calculated, andwheni interpreted in terms of the total radioactiv-ity recovered in the eluate of the Amberlite col-uimn, gave information as to the total amount ofradioactivity of each compound.An aliquot of the IRC-50 effluent containing

70,000 to 80,000 dpm was placed on a 0.9 x 45-cm Dowex-l-acetate column (200 to 400 mesh).tThe column was placed on an automatic fractioncollector and attached to an automatic gradient

t-Calhiochein, Los Angeles, California.

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rwFFigure 2

Sectiotn of sympathetic ganglon. Aoiiyloid deposits (the (lar-k miiaterial) wcere scattered through-out the gaunglia replacing ganglion cells. Ltuxol-fast blte staini, x 550.

Table 2Urinary Output of Noradrenaline andl Adrenalinein Seven Patients wvith Idiopathlic OrthostaticHypotension Compared to That of Eight Patientswith Hypotension Relatedl to Other Diseases

PatientNoradrenaline(jig/24 hi)

Normal range, 25-45

Idiopathic liypotensionL.W. 12.2L.S. 9.4E.O.M. 8.0I.Z. 12.7I.W. 6.8O.G. 8.3M.Q. 0.2Secondary to other diseasesD.A. 29.2M.U. 27.9W.Y. 49.5O.McN. 18.7C.A. 29.6A.R. 21.0B.R. 83.1S.H. 33.9

8.513.412.312.112.87.5

102.512.49.56.94.8

20.513.411.4

eluition system and eltite(1 with amnmnoniuim ace-tate btuffer (pH 4.8) of inc reasinig molarity; 5-mlfractions wer e collected. Throughout the courseof the elutioni, alterniate fractionis xvere assayedfor radioactivity in an automatic low backgroundplanchet couinter. Fractions conistitutin1g singleradioactive peaks were pooled, and the radioac-tivity of the pooledl samples was measured byliquid scintillation.The (daita obtained over the var-iouis collection

Table 3Recovery of Radioactive Noradrenaline Mletabo-lites in Urine Following a One-Minuite IntravenousInject-ion of Noradrenaline 2-1' C: Figures Ex-pressedl as Percentage of the Infused RadioactivityPatienits

Normal rangeL.W.L.S.E.O.M.I.Z.MI.Q.

70 min

19.3 -+- 0.618.525.811.218.618.8

6 hr

53.0 +- 0.840.554.037.338.258.7

24 hr

81.7 ± 1.567.869.555.452.974.9

(irculaion, Volume XXXVI, October 1967

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periods up to 24 hours were compiled and theresults calculated on a General Precision LGP-30 Digital Computer. The metabolic results ofthe orthostatic hypotensive subjects were thencompared to those of normal subjects.

ResultsUrinary Output of Noradrenaline

Of the 15 patients evaluated, seven showedall of the signs and symptoms of idiopathicorthostatic hypotension. These same sevensubjects demonstrated a marked decrease inthe 24-hour urinary output of noradrenaline(table 2); the adrenaline output was nor-mal. Patients with orthostatic hypotension re-lated to other diseases had normal to slightlyelevated levels of urinary noradrenaline andadrenaline.

Noradrenaline Metabolism

Five of these seven patients were injectedwith labeled noradrenaline to evaluate theircapacity to metabolize this sympathetic neu-rohormone. Results of these studies are sum-marized in tables 3 and 4. From these re-sults, it appears that the rate of metabolismof noradrenaline was somewhat less thannormal, since at 70 minutes, 6 hours, and 24hours after injection less radioactivity wasrecovered in these subjects than in normalsubjects during similar periods (table 3).This difference, however, was not sufficientlygreat to permit a definite conclusion of al-tered metabolism. Further, it would appearthat there was a slight decrease in the amountof normetadrenaline glucuronic acid conju-gate (NMC II) and 3, 4-dihydroxyphenyl-glycol sulfate (DOPEG SO4) (table 4) butagain the difference is Qnot sufficiently great toconclude that there was any significant altera-tion in these metabolites. Thus, in subjectswith orthostatic hypoteision, the metabolismof circulating noradrernaline, although slightlydelayed, did not differ greatly from that innormal subjects.

DliscussionIt is generally accepted that noradrenaline

is the neurohormone of the sympatheticnerves23-25 and has a fundamental role inCirculation, Volume XXXVI, October 1967

the regulation of vascular tone.25-31 There-fore, any decrease in sympathetic nerve activityas it relates to the vascular bed would resultin a decrease in vascular tone. These results(table 2) and those of other investigators15-17show that in this form of orthostatic hypoten-sion the amount of circulating or urinary nor-adrenaline or both decreases. Such a deficitcould result from accelerated metabolism, ordecrease in release, or a defect in the biosyn-thesis of this neurohormone. However, theresults of these experiments indicate thatpatients with idiopathic orthostatic hypo-tension metabolize circulating noradrenalinesomewhat more slowly than normal subjects(tables 3 and 4), and this militates against thepossibility of accelerated metabolism. There-fore, it would seem reasonable to conclude thatthe defect in idiopathic orthostatic hypoten-sion is not related to any defect in themetabolism of circulating noradrenaline. Nev-ertheless, the amount of noradrenaline re-covered in the urine of these subjects wasmarkedly reduced (table 2), suggesting thatthe pathogenesis involves either a biosyntheticdefect or a subnormal release, an alteration inmetabolism of endogenous noradrenaline as itis released at the nerve endings, or some com-bination of these.The available data suggest that there may

be an anatomic deficit of efferent sympatheticneurons which would explain the decrease innoradrenaline output and, at the same time,would be compatible with the delay in metab-olism. The only subject, M.Q., on whomanatomic observations were available had de-generation of autonomic ganglia, primarilysympathetic ganglia, and the preganglionicnerves (figs. 1 and 2). Amyloidosis was appar-ently the primary disease and in many areasthere was infiltration around the blood vessels.Nevertheless, the anatomic loss of the neuro-genic structures involved in the synthesis ofnoradrenaline was the most prominent findingand this could explain the subnormal outputof noradrenaline (table 2). The concept ofloss of neurogenic structures,32 34 either due toamyloidosis35 or to other diseases, has been

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Table 4

Excretion Pattern of the Metabolites of Intravenously Injected dl-Noradrenaline During a 70-Minute Postinjec-tion Period and for Six and Twenty-fouir Hours After Injection: Comparison Between Normal Subjects andOrthostatic Hypotensive Patients*

IRC-50 fractionsType ofsubject

Normal0. hypoNormal0. hypoNormal0. hypoNormal0. hypoNormal0. hypoNormal0. hypoNormal0. hypoNormal0. hypoNormal0. hypoNormal0. hypoNormal0. hypoNormal0. hypo

Eluate

77.7 1.974.9 + 5.4

27.0 11.828.7 8.010.8 5.410.8 1.6

6.7 1.28.1± 1.7

6.0 0.6

5.6 0.8

5.3± 0.55.4 2.05.5 0.5

3.8 1.2

3.4 0.5

3.0± 0.6

1.7 0.43.2 0.8

34.0 1.7

24.4 + 1.8

15.1 0.610.4 + 3.0

10.2 0.39.0 0.9

Nor.

49.2 2.549.5 6.2

9.9 7.811.1 4.1

3.8 3.03.5 0.7

1.8 0.81.8 0.8

1.6 0.71.7 0.4

1.4 0.51.2 0.4

1.6 0.41.2 0.4

1.1 + 0.20.8 0.3

0.7 0.3

0.9 0.2

19.3 0.510.8 3.1

8.0 0.1

5.5 0.8

5.3 0.24.2 0.8

Normet.

16.3 1.014.3 0.5

11.1 2.67.5 2.2

4.4 1.33.3 0.6

3.0 0.42.5 0.8

2.4 0.82.0 0.7

2.4 0.41.5 0.4

2.5 0.31.3 0.4

1.6 0.10.8 0.2

0.7 ±0.10.7 0.3

8.7 0.9

5.5 0.8

4.3 0.33.1 + 1.0

3.0 0.22.5 + 0.8

Unk.

4.4 0.26.2 1.6

2.1 0.53.6 1.2

0.8 0.32.5 1.3

0.8 0.22.3 1.0

0.7 0.21.9 0.90.5 0.11.7 0.90.6 0.21.2 + 0.5

0.3 + 0.10.9 0.4

0.3 0.11.1 0.4

2.1 0.13.7 1.5

1.0 0.51.3 0.3

0.7 0.11.8 0.6

Dowex- 1 fractions

NMC 1

0.7 0.10.8 0.2

2.3 0.51.6 +0.5

3.5 1.o2.8 1.1

4.0 3.04.9 1.3

6.3 1.55.2 0.7

3.8 1.46.6 1.0

4.2 4.07.4 2.2

10.7 1.514.7 1.7

23.6 2.025.3 3.8

3.0 0.73.6 0.6

7.3 0.310.4 2.1

12.7 0.113.7 1.3

*Figures are expressed as percentage of the recovered radioactivity + SD.

Abbreviations: Nor. = noradrenaline; normet. = normetadrenaline; unk. unknown; NMC I

NMC II

1.8 0.41.3 + 0.5

3.0 0.11.6 0.9

3.1 1.32.0 0.8

5.8 2.01.8 0.2

2.8 1.13.2 0.8

8.1 1.03.9 2.2

6.5 2.63.4 1.8

6.8 2.33.1 1.1

1.7 1.02.9 1.4

3.7 0.82.4 0.8

6.7 0.43.7 1.8

5.3 0.22.6 0.9

PIBunk.

1.4 0.41.2 0.3

2.8 1.41.9 0.53.5 ± 1.52.8 ± 1.14.5 1.43.6 0.6

6.9 ± 1.04.5 ± 0.9

6.8 ± 1.65.5 0.96.5 ± 1.56.7 ± 1.08.3 ± 2.69.0 2.7

10.5 1.79.0 1.72.9 0.53.5 ± 0.75.2 0.96.8 ± 1.07.3 ± 1.37.2 ± 1.4

normetadrenaline sul-fate; NMC II = normetadrenaline glucuronide; PIB unk. =unknown; MOMA= 3-methoxy-4-hydroxymandelic acid;DOMA 3,4-dihydroxymandelic acid; P3X unk. unknown; VA= vanillic acid; MOPEG SO4 = 3-methoxy-4-hy-droxyphenylglycol sulfate; DOPEG SO4 = 3,4-dihydroxyphenylglycol sulfate; Col. res. column residue.

considered, but the specific metabolic changesof sympathetic efferent neurons and gangliahave not hitherto been demonstrated. Themetabolic pattern of noradrenaline excretionof M. Q. was similar to that of the other sub-jects in this group (table 4), and thereforesuggests that they too may well have sympa-

thetic neuron degeneration.

AcknowledgmentWe are indebted to Dr. Margaret Jones, Depart-

ment of Pathology, Medical College of Virginia,Richmond, Virginia, for preparing the slides shownin figures 1 and 2, and the following physiciansfor permitting us to study their patients: Dr. HenryWagner, Johns Hopkins Hospital; Dr. Harry Mc-

Pherson, Duke Hospital; Dr. Joel Levin, PassavantHospital; Dr. Robert Gilbertson, University of Ten-nessee Hospital; and Major Fred Ten Eyck, USAF,Wright-Patterson AFB.

References1. BRADBURY, S., AND EGGLESTON, C.: Postural

hypotension: Report of three cases. AmerHeart J 1: 73, 1925.

2. ELLIS, L. B., AND HAYNES, F. W.: Posturalhypotension with particular reference to itsoccurrence in disease of central nervous sys-

tem. Arch Intern Med 58: 773, 1936.3. JOHNSON, D. A., ROTH, G. M., AND CRAIG,

W. McK.: Orthostatic hypotension followingchordotomy for intractable pain. Mayo ClinProc 27: 7, 131, 1952.

Circulation, Volume XXXVI, October 1967

Timecollected

0-10Min

10-20Min

20-30Min

30-40Min

40-50Min

50-60Min

60-70Min

1-6Hr

6-24Hr

70 Minpool

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F3Xunk.

0.8 0.50.7 0.42.2 0.41.9 ± 0.32.5 0.72.9 ± 1.22.9 0.62.7± 1.13.7 0.52.2 ± 1.03.8 0.92.7 ± 0.63.8 ± 0.83.0 ± 0.73.9 ± 1.02.7 ± 1.25.5 ± 1.63.3 1.51.9 0.22.2 ± 0.52.7 0.22.5 ± 0.83.4 0.13.1 ± 0.7

Dowex-1 fractions

VA

0.9 0.31.1 0.2

2.0 0.42.8 1.2

2.9 0.91.8 0.6

3.3 0.52.6 0.3

3.4 0.33.4 1.2

4.1 0.83.7 0.6

4.0 1.0

3.8 1.3

3.9 0.94.2 0.8

4.3 1.23.6 1.4

2.0± 1.02.8 0.8

3.1 0.6

3.7 0.8

3.8 0.53.7 0.8

MOPEG S04

1.3 0.11.8 0.8

5.5 2.44.9 1.3

7.7 2.16.1 1.8

9.2 1.58.8 2.0

9.3 1.09.0 2.0

10.8 2.0

9.7 2.1

9.6 0.59.8 3.0

11.2 0.311.2 2.6

10.2 0.612.0 2.7

5.8 1.06.4 1.5

9.2 0.611.6 1.4

9.7 0.510.9± 1.4

4. HICKAM, J. B., AND PRYOR, W. W.: Cardiacoutput in postural hypotension. J Clin Invest30: 401, 1951.

5. BJURE, A., AND LAURELL, H.: Abnormal staticcirculatory phenomena and their symptoms:Arterial orthostatic anemia as a neglectedclinical picture. Upsala Lik Fdren Forh 33:1, 1927.

6. NYLIN, G., AND LEVANDER, M.: Studies on cir-culation with the aid of tagged erythrocytesin case of orthostatic hypotension (asym-pathicotonic hypotension). Ann Intern Med28: 723, 1948.

7. GHRIST, D. G.: Postural hypotension. Mayo ClinProc 2: 117, 1927.

8. CORCORAN, A. C., BROWNING, J. S., AND PAGE,I. H.: Renal hemodynamics in orthostatichypotension: Effects of angiotonin and head-up bed. JAMA 119: 793, 1942.

9. SIEKER, H. O., BURNUM, J. F., HicKAM, J. B.,AND PENROD, K. E.: Treatment of posturalhypotension with counter-pressure garment.JAMA 161: 132, 1956.

Circulation, Volume XXXVI, October 1967

10. WAGNER, H. N., JR.,Pressor effect of the

AND BRAUNWALD, E.:antidiuretic principle

of posterior pituitary in orthostatic hypotension.J Clin Invest 35: 1412, 1956.

1 1. PAGE, E. B., HICKAM, J. B., SIEKER, H. O.,MCINTOSH, H. D., AND PRYOR, W. W.: Reflexvenomotor activity in normal persons and inpatients with postural hypotension. Circulation11: 262, 1955.

12. WAGNER, H. N., JR.: Orthostatic hypotension.Bull Hopkins Hosp 1959.

13. SUNDIN, T.: Effect of body posture on urinaryexcretion of adrenaline and noradrenaline.Acta Med Scand 161 (suppl. 336): 1, 1958.

14. SmTEAD, E. A., JR., AND EBERT, R. V.: Posturalhypotension: Disease of the sympatheticnervous system. Arch Intern Med 67: 546,1941.

15. LuFr, R., AND VON EULER, U. S.: Two cases

of postural hypotension showing a deficiencyin release of norepinephrine and epinephrine.J Clin Invest 32: 1065, 1953.

495

MOMA

7.2 2.213.4 1.0

41.4 8.042.4 6.3

52.3 1.057.1 4.9

51.3 1.0

52.3 5.4

50.8 1.050.4 4.6

47.9 2.148.8 4.8

46.6 1.148.5 2.1

36.9 2.538.8 3.9

27.4 2.527.4 4.7

34.5 0.142.5 4.5

35.4 1.2

40.1 5.2

31.9 1.536.4 2.5

DOMA

1.9 0.51.8 0.4

2.3 0.83.8 1.1

1.1 0.21.8 0.5

1.3 0.41.5 0.6

1.3 0.41.2 0.3

1.3 0.52.4 0.9

2.2 1.62.1 1.2

0.9 0.2

1.5 0.7

2.8 1.62.3 1.0

1.8 + 0.3

1.8 0.41.3 0.31.2 0.3

1.6 0.61.5 0.3

DOPEG S04

1.9 0.41.2 0.3

5.8 1.6

3.5 0.7

6.7 2.04.9 0.3

7.7 1.55.7 1.0

8.3± 1.3

4.8± 1.8

7.2 1.25.2 1.3

8.0 2.0

4.8 0.8

7.1 2.14.2 1.7

7.3 2.25.4 1.6

5.3 1.0

4.2 0.6

7.4 1.34.1 0.5

7.9 1.34.7 1.5

Col. res.

0.8 0.21.6 0.4

1.7 0.42.0 0.3

1.9 0.42.4 ± 1.4

1.5 0.12.2 0.8

2.1 1.03.8 1.8

1.7 0.33.5 0.7

1.5 0.5

2.9 0.8

2.6 1.0

2.3 1.2

2.9 1.12.9 0.8

1.5 0.32.6 0.7

2.5 0.62.6 0.9

2.9 0.72.8 0.9

L)owexEFF II

3.8 0.93.4 0.84.1 0.84.3 ± 1.13.9 0.13.2 0.93.5 0.53.3 0.93.0 0.83.1 ± 0.82.5 0.83.4 ± 1.03.1 ± 1.03.3 ± 1.83.6 ± 1.83.1 0.61.9 0.22.3 ± 0.53.5 0.43.9 0.83.9 ± 1.13.4 0.63.3 0.92.8 0.4

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16. BARNETT, H. C., HAMILTON, M. D., AND KAY,H. B.: Severe orthostatic hypotension. AustAnn Med 4: 183, 1955.

17. HICKLER, R. B., WELLS, R. E., JR., TYLER, H. R.,AND HAMLIN, J. T., III: Plasma catechol amineand EEG responses to acute postural change:Evidence of a deficient pressor amine responsein postural hypotension. Amer J Med 26: 410,1959.

18. GOODALL, MCC., MCCALLY, MICHAEL, ANDGRAVELINE, D. E.: Urinary adrenaline andnoradrenaline response to simulated weight-less state. Amer J Physiol 206: 431, 1964.

19. VON EULER, U. S., AND HELLNER, S.: Nor-adrenaline excretion in muscular work. ActaPhysiol Scand 26: 183, 1952.

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