Institute of Endocrinology and Department of Internal Medicine, Chaim Sheba Medical Center, Tel-Hashomer. Israel

ANGIOTENSIN II AND K CHALLENGE FOLLOWING PROLONGED ACTH ADMINISTRATION TO NORMAL

SUBJECTS

By Z. Kraiem,

T. Rosenthal, R. Rotzak

and B.

Lunenfeld

ABSTRACT

healthy male volunteers on a normal Na and K intake and ambulatory received ACTH (40 IU, im) twice daily for 5 days followed by 2 days of angiotensin II (5\p=n-\13ng/kg body weight/min for 60 min) or oral K citrate (30 mEq./h\m=x\3). A discordance in the aldosterone-stimulating and pressor responses of angiotensin II was unmasked with only the latter response being positive following ACTH-induced refractoriness. K loading was a much more potent natriuretic stimulus than angiotensin II treatment. In contrast to angiotensin II, K could selectively enhance aldosterone secretion by overcoming the inhibition in secretion of the mineralocorticoid induced by prolonged ACTH exposure. Twelve

Three

principal agents are generally recognized to play determinant roles in regulating aldosterone secretion: angiotensin , and ACTH. Whereas angio¬ tensin II and raise aldosterone levels for as long as the stimulus is applied, ACTH, as

well

on

as

cotrophin

the other hand, promotes an initial rise in secretion of aldosterone cortisol, with only the latter being sustained under continued corti-

administration

(Laragh

et

al.

1973).

') Present address: Isotope Institute, Carmel Hospital, Haifa, Israel. To whom reprint requests should be addressed. 2) Part of M. D. Thesis, Sackler School of Medicine, Tel Aviv University, Tel Aviv,

Israel. 3) Established

Investigator

of the Chief Scientifist's Bureau,

Ministry

of Health, Israel.

The aim of the present investigation was to determine whether the human adrenal gland having reached the corticotrophin-induced refractory state with respect to aldosterone secretion would respond to the other major stimuli re¬ gulating secretion of the mineralocorticoid: angiotensin II and K.

MATERIALS AND METHODS

Healthy male volunteers (aged 20-35 years) with informed consent participated in the study. The subjects were maintained on a normal Na and intake (150 and 75 mEq./ day, respectively) and were ambulatory during the study. ACTH (40 IU, Synacthen® gel) was injected im at 8 a. m. and 8 p. m. for 5 con¬ secutive days. Blood was drawn at noon the day before the first ACTH administration ("control day") and on each day (except the 4th) of corticotrophin administration for estimation of aldosterone, cortisol, Na and K. The day following the end of the corticotrophin administration, was given to the subjects.

Angiotensin

II

angiotensin

II

or

infusion (8 subjects)

The protocol was as described by Kaplan Sc Silah (1964). Starting at 8 a.m., a con¬ trol infusion of 5 % glucose was given for Va h. Blood pressure was simultaneously measured to ensure stabilization to a constant value. Angiotensin II (Hypertensin®, Ciba, 0.3 (Mg/ml in 5 % glucose) was then infused for 1 h at a rate (5.1-13.3 ng/kg body weight/min) sufficient to produce an increase in blood pressure measured simul¬ taneously of at least 20 mmHg (diastolic and systolic). The same protocol was re¬ peated on the following day. Blood was sampled at times 0 (i. e. at the start of test), 30 min (i. e. at end of glucose infusion) and 90 min (i. e. at end of angiotensin infusion) for estimation of aldosterone, cortisol, Na and K. —

-

loading (4 subjects) was performed (for 2 consecutive days) as described by Scholer et al. (1973). citrate (30 mEq. in 50 ml water) was given orally at 8 a. m. (time 0) and again after 60 and 120 min. The subjects were under electrocardiogram monitoring during the test. Blood was drawn for estimation of aldosterone, Na and K, at times 0, 60, 120, 180 and 240 min of the loading. tests caused In our experience also the above protocols lor the angiotensin II and significant elevations in aldosterone when performed in normal, healthy subjects who were not given prior ACTH treatment (5.1 ± 0.9 to 26.2 ± 2.1 and 8.3 ± 1.1 to 32.6 + 2.5 ng/100 ml plasma, respectively). Daily urine collections, including the day following the angiotensin II infusion and loading test ("withdrawal day"), were made for estimation of aldosterone, Na and K. Urinary fractionated corticosteroids were determined on control, first and last day of ACTH administration and second day of angiotensin II infusion or loading test.

The test

Laboratory

methods

Na and were measured by flame photometry, cortisol by the fluorimetrie method of De Moor et al. (1960), and plasma and urinary aldosterone by radioimmunoassay using essential the method described by Vetter et al. (1973 ,b), with an aldosterone

Dr. F. Kohen (Dept. of Hormone Research, Weizmann Institute and Miles-Yeda, Ltd., Israel). The following fractionated corticosteroids were estimated colorimetrically following their separation by thin-layer chromatography, as described by Kraiem et al. (1969): metabolites: THB + allo-THB + THA: F

Angiotensin II and K challenge following prolonged ACTH administration to normal subjects.

Institute of Endocrinology and Department of Internal Medicine, Chaim Sheba Medical Center, Tel-Hashomer. Israel ANGIOTENSIN II AND K CHALLENGE FOLLO...
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