Studies on the mechanism by which ACTH stimulates renin activity and angiotensin II formation in man

Abstract. Ten IU of ACTH (1–24) per day was infused for 34 h (starting at 7 a.m.) into 8 normal men on a constant diet containing 135 mm Na+ per day. All subjects retained between 152 and 181 mm of sodium. Potassium balance was negative. Plasma renin activity (PRA) and plasmaangiotensin II (P-A II) started to rise in most subjects after 6 to 8 h of infusion, reached a maximum after 24 h and then tended to decline. As shown previously, the rise in PRA is not due to a rise in plasma renin substrate concentration. Systolic, but not diastolic blood pressure increased significantly on the second day of ACTH-infusion. Plasma cortisol (P-F) was continuously stimulated by ACTH. Plasma aldosterone (P-aldo) increased rapidly 1 h after ACTH administration, then tended to fall, and increased again in most subjects, roughly in parallel with PRA. No significant changes in electrolyte balance, PRA, P-A II, P-F and P-aldo occurred in 3 subjects receiving 'sham'-infusions. Additional experiments in subjects treated with propranolol or indomethacin allowed the conclusion that the effect of ACTH on PRA and P-A II is not mediated by renal beta-adrenergic receptors, but perhaps (partially?) by prostaglandins. Since the infusion rate of ACTH was not much higher than the secretion rate of ACTH in the early morning hours, it is possible that ACTH is physiologically involved in the regulation of renin secretion.

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COMBINATION CONTRACEPTIVE EFFECTS ON MONTHLY CYCLE OF PLASMA ALDOSTERONE, RENIN ACTIVITY AND RENIN SUBSTRATE

Acta Endocrinologica ◽

10.1530/acta.0.0790295 ◽

1975 ◽

Vol 79 (2) ◽

pp. 295-300 ◽

Cited By ~ 6

Author(s):

Fred H. Katz ◽

Peggy Romfh ◽

Judith A. Smith ◽

Ellen F. Roper ◽

John S. Barnes

Keyword(s):

Luteal Phase ◽

Plasma Cortisol ◽

Plasma Renin ◽

Plasma Aldosterone ◽

Renin Activity ◽

Normal Range ◽

Renin Substrate ◽

Oral Contraceptive Pills ◽

Contraceptive Pills ◽

Menstruating Women

ABSTRACT A post-ovulatory peak of fasting supine plasma aldosterone (PA) preceded or accompanied by an increase in plasma renin activity (PRA) was previously reported. These studies have now been extended in 4 additional normal menstruating women and 4 women taking oestrogen-progestogen oral contraceptive pills (OCP), all studied daily for an entire cycle. Distinct luteal phase increases in PRA were seen in the 4 normals, with 2 also demonstrating a rise in PA. Plasma renin substrate (PRS) was usually unvarying throughout the control cycles. The women taking OCP, on the other hand, all had PA and PRA peaks that were apparent by the fourth or fifth day of taking "the pill". All 4 of the treated women had elevated PRS levels but only one woman showed an increase which preceded the elevation of PRA and PA. Plasma cortisol levels were usually above the normal range in the women taking OCP. This study thus indicates that factors other than oestrogen-induced increased substrate production may be responsible for the PRA and PA rise during OCP treatment Such factors might be the natri-uretic effects of oestrogens and progestogens or a direct effect on renin secretion by one of these steroids.

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Renin, aldosterone, electrolyte, and cortisol responses to hypoxic decompression

Journal of Applied Physiology ◽

10.1152/jappl.1977.43.3.421 ◽

1977 ◽

Vol 43 (3) ◽

pp. 421-424 ◽

Cited By ~ 30

Author(s):

J. R. Sutton ◽

G. W. Viol ◽

G. W. Gray ◽

M. McFadden ◽

P. M. Keane

Keyword(s):

Plasma Renin Activity ◽

Plasma Cortisol ◽

Acute Mountain Sickness ◽

Plasma Renin ◽

Plasma Aldosterone ◽

Renin Activity ◽

Plasma Sodium ◽

Plasma Aldosterone Concentration ◽

Urinary Potassium ◽

Mountain Sickness

Responses of plasma renin activity, plasma aldosterone, plasma cortisol, and plasma electrolyte concentration and urinary electrolyte and aldosterone excretion were studied in four men during hypoxic decompression to a stimulated altitude of 4,760 m in a pressure chamber. Three of the four subjects developed significant acute mountain sickness. Plasma sodium and potassium concentrations were unchanged. No significant change in plasma renin activity was observed, but values tended to fall. Plasma aldosterone concentration was depressed while plasma cortisol was elevated and diurnal variation lost. Urinary sodium excretion was unchanged, but urinary potassium and aldosterone excretion were decreased. The decrease in plasma and urinary aldosterone and urinary potassium in the absence of change in plasma renin activity or plasma potassium is of uncertain origin. It is unlikely to be due to a decrease in adrenocorticotropin secretion since plasma cortisol rose during the same time. None of the changes could be causally implicated in the development of acute mountain sickness although the increase in plasma cortisol was greatest in the most ill.

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DIURNAL VARIATIONS OF PLASMA ALDOSTERONE IN SUPINE MAN: RELATIONSHIP TO PLASMA RENIN ACTIVITY AND PLASMA CORTISOL

Acta Endocrinologica ◽

10.1530/acta.0.0800095 ◽

1975 ◽

Vol 80 (1) ◽

pp. 95-103 ◽

Cited By ~ 43

Author(s):

Helmut Armbruster ◽

Wilhelm Vetter ◽

Rainer Beckerhoff ◽

Jürg Nussberger ◽

Hans Vetter ◽

...

Keyword(s):

Plasma Renin Activity ◽

Plasma Cortisol ◽

Sodium Intake ◽

Plasma Concentrations ◽

Renin Angiotensin System ◽

Plasma Renin ◽

Plasma Aldosterone ◽

Renin Activity ◽

Dominant Factor ◽

Sodium Restriction

ABSTRACT In order to investigate the role of renin secretion and of ACTH on the circadian rhythm of plasma aldosterone (PA), plasma renin activity (PRA), plasma cortisol (PC) and PA were determined at short-time intervals in 10 normal supine men. Six subjects were studied under a normal sodium intake and 4 under sodium restriction. In 4 subjects the secretion of ACTH was suppressed by dexamethasone. Under normal sodium intake changes in PA seemed to be more in parallel with changes in PC than by those in PRA as indicated by a higher significant correlation between PA and PC than between PA and PRA in 3 of the 4 subjects. In 1 subject no correlation was observed between PA and PC despite visual synchronism between the plasma concentrations of both hormones. Under dexamethasone medication fluctuations in PA were followed by those in PRA while PC was less than 2 μg/100 ml. In the sodium restricted state, changes in PA were closely paralleled and significantly correlated to PRA while no correlation was seen between PA and PC. Under dexamethasone medication the significant correlation between PA and PRA persisted. Our results indicate that in normal supine man the influence of ACTH and renin on PA may vary with different sodium intakes. Under normal sodium intake ACTH seems to be the dominant factor controlling PA, whereas under sodium restriction changes in PA are mediated through the renin angiotensin system. When the secretion of ACTH is suppressed by dexamethasone, renin controls PA both under normal and low sodium intake.

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Infusion of iso-rANP(1–45) or (17–45) increases plasma immunoreactive ANP and lowers plasma renin activity and aldosterone

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y90-194 ◽

1990 ◽

Vol 68 (9) ◽

pp. 1292-1297 ◽

Cited By ~ 4

Author(s):

D. B. Jennings ◽

J. C. McKirdy ◽

P. J. Ohtake ◽

I. R. Sarda ◽

T. G. Flynn ◽

...

Keyword(s):

Plasma Renin Activity ◽

Plasma Renin ◽

Plasma Aldosterone ◽

Renin Activity ◽

Electrolyte Balance ◽

Factors Influencing ◽

Water And Electrolyte Balance ◽

Anp Receptors ◽

Renal Responses ◽

Stimulation Of

We have reported that a second rat atrial natriuretic peptide, iso-rANP(1–45), as well as the putative ANP homologue, iso-rANP(17–45), elicited circulatory and renal responses in the rat similar to those found after administration of ANP. Iso-rANP also interacted with ANP to potentiate the observed biological activity in the rat. In the present studies in awake dogs, intravenous infusion of low doses (6.3–50 pmol∙kg−1∙min−1) of iso-rANP(1–45) and iso-rANP(17–45) increased plasma immunoreactive ANP and suppressed plasma renin activity (PRA) and aldosterone. Iso-rANP, like ring-deleted analogues of ANP, may have displaced ANP from ANP clearance receptors to increase plasma ANP concentration, since factors influencing myocardial ANP release were not changed. The effect of iso-rANP(1–45) and (17–45) in lowering PRA and plasma aldosterone may therefore have been indirect, via ANP stimulation of active guanylate cyclase-linked ANP receptors. However, an additional direct effect of iso-rANP on an active receptor cannot be excluded.Key words: clearance and active ANP receptors, arginine vasopressin, water and electrolyte balance, circulatory hemodynamics.

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Evidence for two independent effects of oestradiol benzoate on the renin-angiotensin-aldosterone system

Acta Endocrinologica ◽

10.1530/acta.0.1000077 ◽

1982 ◽

Vol 100 (1) ◽

pp. 77-84 ◽

Cited By ~ 2

Author(s):

Helmut Kaulhausen ◽

Cornelia Weyand

Keyword(s):

Time Course ◽

Plasma Renin ◽

Plasma Aldosterone ◽

Renin Activity ◽

Renin Substrate ◽

Renin Angiotensin Aldosterone System ◽

Plasma Aldosterone Concentration ◽

Renin Angiotensin ◽

Oestradiol Benzoate ◽

Independent Effects

Abstract. Plasma renin concentrations (PRC), plasma renin substrate concentration (PRS), plasma aldosterone and cortisol concentrations as well as plama renin activity (PRA) were measured in ovariectomized subjects after im administration of 10 mg oestradiol benzoate (EB). The esterified oestrogen exerts two independent effects on the renin-angiotensin-aldosterone system. 1) 48 h after EB administration, PRS was significantly increased. Similar results were obtained for total plasma cortisol, reflecting transcortin concentration. In both cases, the increase was quantitatively related to the basal concentrations. These observations are consistent with the well known oestrogen-induced protein synthesis in the liver. 2) The elevation of PRC preceded that of PRS and was already significant 11 h after EB injection. The early rise in plasma renin activity was essentially caused by the increase in PRC, whereas an influence of the activated substrate synthesis was found later, between the 2nd and the 4th day post injection. The time course of plasma aldosterone concentration correlated well with the increased PRA. The results provide evidence that EB has two different effects on the renin-aldosterone axis: an early one by elevating renin release and a delayed one by increasing renin substrate synthesis. Whereas the second mechanism can clearly be localized in the liver, extrarenal as well as direct renal effects of EB may be responsible for the renin stimulation.

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Biological Activity of Angiotensin II-(4-8)-Pentapeptide in Man

Clinical Science ◽

10.1042/cs063195s ◽

1982 ◽

Vol 63 (s8) ◽

pp. 195s-197s ◽

Cited By ~ 1

Author(s):

T. Kono ◽

F. Oseko ◽

F. Ikeda ◽

H. Imura ◽

M. C. Khosla ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Plasma Renin Activity ◽

Plasma Renin ◽

Plasma Aldosterone ◽

Renin Activity ◽

Bartter's Syndrome ◽

Pressure Plasma ◽

Significant Change ◽

Normal Men

1. When the angiotensin II-(4-8)-pentapeptide was infused intravenously at rates of 0.31-5.55 nmol min−1 kg−1 for 10–120 min into five normal men or two patients with Bartter's syndrome, no significant change was observed in blood pressure, plasma renin activity and plasma aldosterone, and the lowest dose did not inhibit the captopril-induced increase in plasma renin activity in the normal men. 2. An intravenous infusion of the pentapeptide at 9–0 nmol min−1 kg−1 for 15 min significantly raised blood pressure in the five normal men but not in patients with Bartter's syndrome. Blood pressure returned to the pre-treatment level 60 min after the cessation of the infusion in the normal men. 3. At the same dose level none of the seven subjects examined showed any significant change in plasma renin activity and plasma aldosterone. 4. Angiotensin II-(5-8)-tetrapeptide was infused intravenously into one of the normal men at a rate of 41.5 nmol min−1 kg−1 for 15 min, but it caused no significant change in blood pressure, plasma renin activity and plasma aldosterone. 5. These results suggest that the pentapeptide and probably the tetrapeptide do not possess renin-suppressing and steroidogenic actions in man but that the former peptide does elicit a modest pressor action with a prolonged duration.

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Biological activity of des-asp-,des-arg-angiotensin II in man

Acta Endocrinologica ◽

10.1530/acta.0.0990577 ◽

1982 ◽

Vol 99 (4) ◽

pp. 577-584 ◽

Cited By ~ 6

Author(s):

Tsuyoshi Kono ◽

Fumitake Ikeda ◽

Fumimaro Oseko ◽

Yoshiaki Ohmori ◽

Ryuichi Nakano ◽

...

Keyword(s):

Blood Pressure ◽

Biological Activity ◽

Angiotensin Ii ◽

Plasma Renin Activity ◽

Plasma Renin ◽

Plasma Aldosterone ◽

Renin Activity ◽

Renin Release ◽

Direct Inhibition ◽

Normal Men

Abstract. The biololgical activity of des-asp1-,des-arg2-angiotensin II (3-8AII) was studied in man. When 3-8AII was infused iv at rates of 22 and 308 pmol (17.5 and 250 ng)/kg · min separately into 5 normal men each for 120 min, blood pressure showed no change, plasma renin activity (PRA) decreased gradually and plasma aldosterone showed a gradual slight increase. The lower dose of 3-8AII partially inhibited captopril-induced PRA increase and plasma aldosterone decrease in the same 5 normal men and the higher dose of the hexapeptide completely abolished them. In one of the 5 normal men blood pressure rose in response to doses of 3-8AII greater than 2220 pmol (1750 ng)/kg · min. When 3-8AII was infused iv at 308 pmol/kg · min into 2 patients with Bartter's syndrome for 60 min, it caused marked decreases in PRA and plasma aldosterone but no change in blood pressure. This decrease in plasma aldosterone is thought to be secondary to the decrease in PRA. From these results it is evident that 3-8AII has a minimal pressor action, a weak aldosterone-stimulating action and a significant renin-suppressing action in man and this PRA-lowering action is thought to be due to direct inhibition of renin release by its whole molecule or a smaller part of the molecule.

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Effect of Propranolol Therapy on Aldosterone Responses to Angiotensin II and Adrenocorticotropic Hormone in Essential Hypertension

Clinical Science ◽

10.1042/cs0610107 ◽

1981 ◽

Vol 61 (1) ◽

pp. 107-110 ◽

Cited By ~ 4

Author(s):

M. S. Golub ◽

M. L. Tuck ◽

D. B. Fittingoff

Keyword(s):

Essential Hypertension ◽

Angiotensin Ii ◽

Plasma Renin Activity ◽

Plasma Cortisol ◽

Adrenocorticotropic Hormone ◽

Plasma Renin ◽

Plasma Aldosterone ◽

Renin Activity ◽

Before And After ◽

Propranolol Therapy

1. The plasma aldosterone responses to exogenous angiotensin II and adrenocorticotropic hormone (ACTH) were studied before and after 1 month of propranolol therapy (120–240 mg/day) in eight patients with essential hypertension. 2. Basal supine plasma renin activity was decreased (P < 0.001) after propranolol, whereas plasma aldosterone was unchanged. After 3 h of upright posture the increases in both plasma renin activity and aldosterone were decreased (P < 0.05) after propranolol. 3. Plasma aldosterone responses to exogenous angiotensin II and ACTH were not significantly different after propranolol. Serum and urinary electrolytes and plasma cortisol were also unaffected by propranolol therapy. 4. It is concluded that changes in adrenal sensitivity are not responsible for maintaining unchanged supine plasma aldosterone concentrations after β-adrenoceptor antagonism in essential hypertension.

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VARIATIONS IN PLASMA ALDOSTERONE AND PLASMA RENIN ACTIVITY THROUGHOUT THE MENSTRUAL CYCLE, WITH SPECIAL REFERENCE TO THE PRE-OVULATORY PERIOD

Acta Endocrinologica ◽

10.1530/acta.0.0730499 ◽

1973 ◽

Vol 73 (3) ◽

pp. 499-508 ◽

Cited By ~ 24

Author(s):

Johan A. Sundsfjord ◽

A. Aakvaag

Keyword(s):

Menstrual Cycle ◽

Plasma Renin Activity ◽

Plasma Renin ◽

Blocking Agent ◽

Plasma Aldosterone ◽

Renin Activity ◽

Renin Substrate ◽

Specific Radioimmunoassay ◽

Early Follicular Phase ◽

Ovulatory Period

ABSTRACT The day to day variations in plasma aldosterone and plasma renin activity throughout the menstrual cycle have been investigated in healthy young women. A sensitive and specific radioimmunoassay for the measurement of plasma aldosterone is described. The actual hormone parameters have been correlated with fluctuations in plasma oestradiol and progesterone, and LH has been measured for the determination of time of ovulation. Plasma renin activity and plasma aldosterone gradually increased two to four times from the early follicular to the mid-luteal phase, in accordance with earlier observations. In one woman using a beta adrenergic blocking agent plasma renin activity rose only slightly, whereas a normal rise in plasma aldosterone was noted. Another woman became pregnant during the cycle investigated. In this subject neither plasma renin activity nor plasma aldosterone decreased at the end of the cycle. Plasma aldosterone was almost doubled on the pre-ovulatory day, as compared with the early follicular phase, whereas no significant change in plasma renin activity or plasma renin substrate was found. The cause of this pre-ovulatory increase in plasma aldosterone is not known.

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